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146 results on '"Hilf, Norbert"'

1. A combinatory vaccine with IMA950 plus varlilumab promotes effector memory T-cell differentiation in the peripheral blood of patients with low-grade gliomas

Author

Saijo, Atsuro, Ogino, Hirokazu, Butowski, Nicholas A, Tedesco, Meghan R, Gibson, David, Watchmaker, Payal B, Okada, Kaori, Wang, Albert S, Shai, Anny, Salazar, Andres M, Molinaro, Annette M, Rabbitt, Jane E, Shahin, Maryam, Perry, Arie, Clarke, Jennifer L, Taylor, Jennie W, Daras, Mariza, Bush, Nancy Ann Oberheim, Hervey-Jumper, Shawn L, Phillips, Joanna J, Chang, Susan M, Hilf, Norbert, Mayer-Mokler, Andrea, Keler, Tibor, Berger, Mitchel S, and Okada, Hideho

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Immunology, Brain Cancer, Patient Safety, Immunization, Clinical Research, Prevention, Orphan Drug, Cancer, Vaccine Related, Neurosciences, Brain Disorders, Clinical Trials and Supportive Activities, Biotechnology, Rare Diseases, Immunotherapy, 6.1 Pharmaceuticals, 5.1 Pharmaceuticals, Good Health and Well Being, Humans, Pilot Projects, Leukocytes, Mononuclear, Prospective Studies, Glioma, Cancer Vaccines, Cell Differentiation, Tumor Microenvironment, Peptides, Antibodies, Monoclonal, Humanized, immunotherapy, IMA950, low-grade glioma, poly-ICLC, varlilumab, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundCentral nervous system (CNS) WHO grade 2 low-grade glioma (LGG) patients are at high risk for recurrence and with unfavorable long-term prognosis due to the treatment resistance and malignant transformation to high-grade glioma. Considering the relatively intact systemic immunity and slow-growing nature, immunotherapy may offer an effective treatment option for LGG patients.MethodsWe conducted a prospective, randomized pilot study to evaluate the safety and immunological response of the multipeptide IMA950 vaccine with agonistic anti-CD27 antibody, varlilumab, in CNS WHO grade 2 LGG patients. Patients were randomized to receive combination therapy with IMA950 + poly-ICLC and varlilumab (Arm 1) or IMA950 + poly-ICLC (Arm 2) before surgery, followed by adjuvant vaccines.ResultsA total of 14 eligible patients were enrolled in the study. Four patients received pre-surgery vaccines but were excluded from postsurgery vaccines due to the high-grade diagnosis of the resected tumor. No regimen-limiting toxicity was observed. All patients demonstrated a significant increase of anti-IMA950 CD8+ T-cell response postvaccine in the peripheral blood, but no IMA950-reactive CD8+ T cells were detected in the resected tumor. Mass cytometry analyses revealed that adding varlilumab promoted T helper type 1 effector memory CD4+ and effector memory CD8+ T-cell differentiation in the PBMC but not in the tumor microenvironment.ConclusionThe combinational immunotherapy, including varlilumab, was well-tolerated and induced vaccine-reactive T-cell expansion in the peripheral blood but without a detectable response in the tumor. Further developments of strategies to overcome the blood-tumor barrier are warranted to improve the efficacy of immunotherapy for LGG patients.

Published
2024

2. Identification of Tumor Antigens Among the HLA Peptidomes of Glioblastoma Tumors and Plasma* [S]

Author

Shraibman, Bracha, Barnea, Eilon, Kadosh, Dganit Melamed, Haimovich, Yael, Slobodin, Gleb, Rosner, Itzhak, López-Larrea, Carlos, Hilf, Norbert, Kuttruff, Sabrina, Song, Colette, Britten, Cedrik, Castle, John, Kreiter, Sebastian, Frenzel, Katrin, Tatagiba, Marcos, Tabatabai, Ghazaleh, Dietrich, Pierre-Yves, Dutoit, Valérie, Wick, Wolfgang, Platten, Michael, Winkler, Frank, von Deimling, Andreas, Kroep, Judith, Sahuquillo, Juan, Martinez-Ricarte, Francisco, Rodon, Jordi, Lassen, Ulrik, Ottensmeier, Christian, van der Burg, Sjoerd H, Thor Straten, Per, Poulsen, Hans Skovgaard, Ponsati, Berta, Okada, Hideho, Rammensee, Hans-Georg, Sahin, Ugur, Singh, Harpreet, and Admon, Arie

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Clinical Research, Rare Diseases, Brain Disorders, Neurosciences, Brain Cancer, Cancer, Good Health and Well Being, Alleles, Antigens, Neoplasm, Biomarkers, Tumor, Brain Neoplasms, Glioblastoma, Histocompatibility Antigens Class I, Humans, Peptides, Proteome, CTA, Cancer Biomarker(s), Cancer Therapeutics, HLA, Immunoaffinity, Immunotherapy, MHC, Peptidomics, Plasma or Serum Analysis, Biochemistry & Molecular Biology
Abstract

Glioblastoma multiforme (GBM) is the most aggressive brain tumor with poor prognosis to most patients. Immunotherapy of GBM is a potentially beneficial treatment option, whose optimal implementation may depend on familiarity with tumor specific antigens, presented as HLA peptides by the GBM cells. Further, early detection of GBM, such as by a routine blood test, may improve survival, even with the current treatment modalities. This study includes large-scale analyses of the HLA peptidome (immunopeptidome) of the plasma-soluble HLA molecules (sHLA) of 142 plasma samples, and the membranal HLA of GBM tumors of 10 of these patients' tumor samples. Tumor samples were fresh-frozen immediately after surgery and the plasma samples were collected before, and at multiple visits after surgery. In total, this HLA peptidome analysis involved 52 different HLA allotypes and resulted in the identification of more than 35,000 different HLA peptides. Strong correlations were observed in the signal intensities and in the repertoires of identified peptides between the tumors and plasma-soluble HLA peptidomes of the individual patients, whereas low correlations were observed between these HLA peptidomes and the tumors' proteomes. HLA peptides derived from Cancer/Testis Antigens (CTAs) were selected based on their presence among the HLA peptidomes of the patients and absence of expression of their source genes from any healthy and essential human tissues, except from immune-privileged sites. Additionally, peptides were selected as potential biomarkers if their levels in the plasma-sHLA peptidome were significantly reduced after the removal of tumor mass. The CTAs identified among the analyzed HLA peptidomes provide new opportunities for personalized immunotherapy and for early diagnosis of GBM.

Published
2019

4. A combinatory vaccine with IMA950 plus varlilumab promotes effector memory T-cell differentiation in the peripheral blood of patients with low-grade gliomas

Author

Saijo, Atsuro, primary, Ogino, Hirokazu, additional, Butowski, Nicholas A, additional, Tedesco, Meghan R, additional, Gibson, David, additional, Watchmaker, Payal B, additional, Okada, Kaori, additional, Wang, Albert S, additional, Shai, Anny, additional, Salazar, Andres M, additional, Molinaro, Annette M, additional, Rabbitt, Jane E, additional, Shahin, Maryam, additional, Perry, Arie, additional, Clarke, Jennifer L, additional, Taylor, Jennie W, additional, Daras, Mariza, additional, Oberheim Bush, Nancy Ann, additional, Hervey-Jumper, Shawn L, additional, Phillips, Joanna J, additional, Chang, Susan M, additional, Hilf, Norbert, additional, Mayer-Mokler, Andrea, additional, Keler, Tibor, additional, Berger, Mitchel S, additional, and Okada, Hideho, additional

Published
2023
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6. Actively personalized vaccination trial for newly diagnosed glioblastoma

Author

Hilf, Norbert, Kuttruff-Coqui, Sabrina, Frenzel, Katrin, Bukur, Valesca, Stevanovic, Stefan, Gouttefangeas, Cécile, and Platten, Michael

Subjects
APVAC2 (Vaccine) -- Dosage and administration -- Testing, APVAC1 (Vaccine) -- Dosage and administration -- Testing, Diagnosis, Drug therapy, Testing, Analysis, Dosage and administration, Methods, Precision medicine -- Methods, CD8 lymphocytes -- Analysis, Vaccines -- Dosage and administration -- Testing, Vaccination -- Dosage and administration, CD4 lymphocytes -- Analysis, Glioblastomas -- Diagnosis -- Drug therapy
Abstract

Author(s): Norbert Hilf [sup.1] , Sabrina Kuttruff-Coqui [sup.1] , Katrin Frenzel [sup.2] , Valesca Bukur [sup.2] , Stefan Stevanovic [sup.3] [sup.4] , Cécile Gouttefangeas [sup.3] [sup.4] [sup.5] , Michael Platten [...], Patients with glioblastoma currently do not sufficiently benefit from recent breakthroughs in cancer treatment that use checkpoint inhibitors.sup.1,2. For treatments using checkpoint inhibitors to be successful, a high mutational load and responses to neoepitopes are thought to be essential.sup.3. There is limited intratumoural infiltration of immune cells.sup.4 in glioblastoma and these tumours contain only 30-50 non-synonymous mutations.sup.5. Exploitation of the full repertoire of tumour antigens--that is, both unmutated antigens and neoepitopes--may offer more effective immunotherapies, especially for tumours with a low mutational load. Here, in the phase I trial GAPVAC-101 of the Glioma Actively Personalized Vaccine Consortium (GAPVAC), we integrated highly individualized vaccinations with both types of tumour antigens into standard care to optimally exploit the limited target space for patients with newly diagnosed glioblastoma. Fifteen patients with glioblastomas positive for human leukocyte antigen (HLA)-A*02:01 or HLA-A*24:02 were treated with a vaccine (APVAC1) derived from a premanufactured library of unmutated antigens followed by treatment with APVAC2, which preferentially targeted neoepitopes. Personalization was based on mutations and analyses of the transcriptomes and immunopeptidomes of the individual tumours. The GAPVAC approach was feasible and vaccines that had poly-ICLC (polyriboinosinic-polyribocytidylic acid-poly-l-lysine carboxymethylcellulose) and granulocyte-macrophage colony-stimulating factor as adjuvants displayed favourable safety and strong immunogenicity. Unmutated APVAC1 antigens elicited sustained responses of central memory CD8.sup.+ T cells. APVAC2 induced predominantly CD4.sup.+ T cell responses of T helper 1 type against predicted neoepitopes. In a phase I trial, highly individualized peptide vaccines against unmutated tumour antigens and neoepitopes elicited sustained responses in CD8.sup.+ and CD4.sup.+ T cells, respectively, in patients with newly diagnosed glioblastoma.

Published
2019
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7. Supplemental Figure 10 from Feasibility and Safety of Personalized, Multi-Target, Adoptive Cell Therapy (IMA101): First-in-Human Clinical Trial in Patients with Advanced Metastatic Cancer

Author

Tsimberidou, Apostolia M., primary, Guenther, Kerstin, primary, Andersson, Borje S., primary, Mendrzyk, Regina, primary, Alpert, Amir, primary, Wagner, Claudia, primary, Nowak, Anna, primary, Aslan, Katrin, primary, Satelli, Arun, primary, Richter, Fabian, primary, Kuttruff-Coqui, Sabrina, primary, Schoor, Oliver, primary, Fritsche, Jens, primary, Coughlin, Zoe, primary, Mohamed, Ali S., primary, Sieger, Kerry, primary, Norris, Becky, primary, Ort, Rita, primary, Beck, Jennifer, primary, Vo, Henry Hiep, primary, Hoffgaard, Franziska, primary, Ruh, Manuel, primary, Backert, Linus, primary, Wistuba, Ignacio I., primary, Fuhrmann, David, primary, Ibrahim, Nuhad K., primary, Morris, Van Karlyle, primary, Kee, Bryan K., primary, Halperin, Daniel M., primary, Nogueras-Gonzalez, Graciela M., primary, Kebriaei, Partow, primary, Shpall, Elizabeth J., primary, Vining, David, primary, Hwu, Patrick, primary, Singh, Harpreet, primary, Reinhardt, Carsten, primary, Britten, Cedrik M., primary, Hilf, Norbert, primary, Weinschenk, Toni, primary, Maurer, Dominik, primary, and Walter, Steffen, primary

Published
2023
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8. Data from Feasibility and Safety of Personalized, Multi-Target, Adoptive Cell Therapy (IMA101): First-in-Human Clinical Trial in Patients with Advanced Metastatic Cancer

Author

Tsimberidou, Apostolia M., primary, Guenther, Kerstin, primary, Andersson, Borje S., primary, Mendrzyk, Regina, primary, Alpert, Amir, primary, Wagner, Claudia, primary, Nowak, Anna, primary, Aslan, Katrin, primary, Satelli, Arun, primary, Richter, Fabian, primary, Kuttruff-Coqui, Sabrina, primary, Schoor, Oliver, primary, Fritsche, Jens, primary, Coughlin, Zoe, primary, Mohamed, Ali S., primary, Sieger, Kerry, primary, Norris, Becky, primary, Ort, Rita, primary, Beck, Jennifer, primary, Vo, Henry Hiep, primary, Hoffgaard, Franziska, primary, Ruh, Manuel, primary, Backert, Linus, primary, Wistuba, Ignacio I., primary, Fuhrmann, David, primary, Ibrahim, Nuhad K., primary, Morris, Van Karlyle, primary, Kee, Bryan K., primary, Halperin, Daniel M., primary, Nogueras-Gonzalez, Graciela M., primary, Kebriaei, Partow, primary, Shpall, Elizabeth J., primary, Vining, David, primary, Hwu, Patrick, primary, Singh, Harpreet, primary, Reinhardt, Carsten, primary, Britten, Cedrik M., primary, Hilf, Norbert, primary, Weinschenk, Toni, primary, Maurer, Dominik, primary, and Walter, Steffen, primary

Published
2023
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9. Supplemental Figure 9 from Feasibility and Safety of Personalized, Multi-Target, Adoptive Cell Therapy (IMA101): First-in-Human Clinical Trial in Patients with Advanced Metastatic Cancer

Author

Tsimberidou, Apostolia M., primary, Guenther, Kerstin, primary, Andersson, Borje S., primary, Mendrzyk, Regina, primary, Alpert, Amir, primary, Wagner, Claudia, primary, Nowak, Anna, primary, Aslan, Katrin, primary, Satelli, Arun, primary, Richter, Fabian, primary, Kuttruff-Coqui, Sabrina, primary, Schoor, Oliver, primary, Fritsche, Jens, primary, Coughlin, Zoe, primary, Mohamed, Ali S., primary, Sieger, Kerry, primary, Norris, Becky, primary, Ort, Rita, primary, Beck, Jennifer, primary, Vo, Henry Hiep, primary, Hoffgaard, Franziska, primary, Ruh, Manuel, primary, Backert, Linus, primary, Wistuba, Ignacio I., primary, Fuhrmann, David, primary, Ibrahim, Nuhad K., primary, Morris, Van Karlyle, primary, Kee, Bryan K., primary, Halperin, Daniel M., primary, Nogueras-Gonzalez, Graciela M., primary, Kebriaei, Partow, primary, Shpall, Elizabeth J., primary, Vining, David, primary, Hwu, Patrick, primary, Singh, Harpreet, primary, Reinhardt, Carsten, primary, Britten, Cedrik M., primary, Hilf, Norbert, primary, Weinschenk, Toni, primary, Maurer, Dominik, primary, and Walter, Steffen, primary

Published
2023
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10. Supplemental Figure 4 from Feasibility and Safety of Personalized, Multi-Target, Adoptive Cell Therapy (IMA101): First-in-Human Clinical Trial in Patients with Advanced Metastatic Cancer

Author

Tsimberidou, Apostolia M., primary, Guenther, Kerstin, primary, Andersson, Borje S., primary, Mendrzyk, Regina, primary, Alpert, Amir, primary, Wagner, Claudia, primary, Nowak, Anna, primary, Aslan, Katrin, primary, Satelli, Arun, primary, Richter, Fabian, primary, Kuttruff-Coqui, Sabrina, primary, Schoor, Oliver, primary, Fritsche, Jens, primary, Coughlin, Zoe, primary, Mohamed, Ali S., primary, Sieger, Kerry, primary, Norris, Becky, primary, Ort, Rita, primary, Beck, Jennifer, primary, Vo, Henry Hiep, primary, Hoffgaard, Franziska, primary, Ruh, Manuel, primary, Backert, Linus, primary, Wistuba, Ignacio I., primary, Fuhrmann, David, primary, Ibrahim, Nuhad K., primary, Morris, Van Karlyle, primary, Kee, Bryan K., primary, Halperin, Daniel M., primary, Nogueras-Gonzalez, Graciela M., primary, Kebriaei, Partow, primary, Shpall, Elizabeth J., primary, Vining, David, primary, Hwu, Patrick, primary, Singh, Harpreet, primary, Reinhardt, Carsten, primary, Britten, Cedrik M., primary, Hilf, Norbert, primary, Weinschenk, Toni, primary, Maurer, Dominik, primary, and Walter, Steffen, primary

Published
2023
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11. Supplemental Figure 3 from Feasibility and Safety of Personalized, Multi-Target, Adoptive Cell Therapy (IMA101): First-in-Human Clinical Trial in Patients with Advanced Metastatic Cancer

Author

Tsimberidou, Apostolia M., primary, Guenther, Kerstin, primary, Andersson, Borje S., primary, Mendrzyk, Regina, primary, Alpert, Amir, primary, Wagner, Claudia, primary, Nowak, Anna, primary, Aslan, Katrin, primary, Satelli, Arun, primary, Richter, Fabian, primary, Kuttruff-Coqui, Sabrina, primary, Schoor, Oliver, primary, Fritsche, Jens, primary, Coughlin, Zoe, primary, Mohamed, Ali S., primary, Sieger, Kerry, primary, Norris, Becky, primary, Ort, Rita, primary, Beck, Jennifer, primary, Vo, Henry Hiep, primary, Hoffgaard, Franziska, primary, Ruh, Manuel, primary, Backert, Linus, primary, Wistuba, Ignacio I., primary, Fuhrmann, David, primary, Ibrahim, Nuhad K., primary, Morris, Van Karlyle, primary, Kee, Bryan K., primary, Halperin, Daniel M., primary, Nogueras-Gonzalez, Graciela M., primary, Kebriaei, Partow, primary, Shpall, Elizabeth J., primary, Vining, David, primary, Hwu, Patrick, primary, Singh, Harpreet, primary, Reinhardt, Carsten, primary, Britten, Cedrik M., primary, Hilf, Norbert, primary, Weinschenk, Toni, primary, Maurer, Dominik, primary, and Walter, Steffen, primary

Published
2023
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12. Supplemental Figure 6 from Feasibility and Safety of Personalized, Multi-Target, Adoptive Cell Therapy (IMA101): First-in-Human Clinical Trial in Patients with Advanced Metastatic Cancer

Author

Tsimberidou, Apostolia M., primary, Guenther, Kerstin, primary, Andersson, Borje S., primary, Mendrzyk, Regina, primary, Alpert, Amir, primary, Wagner, Claudia, primary, Nowak, Anna, primary, Aslan, Katrin, primary, Satelli, Arun, primary, Richter, Fabian, primary, Kuttruff-Coqui, Sabrina, primary, Schoor, Oliver, primary, Fritsche, Jens, primary, Coughlin, Zoe, primary, Mohamed, Ali S., primary, Sieger, Kerry, primary, Norris, Becky, primary, Ort, Rita, primary, Beck, Jennifer, primary, Vo, Henry Hiep, primary, Hoffgaard, Franziska, primary, Ruh, Manuel, primary, Backert, Linus, primary, Wistuba, Ignacio I., primary, Fuhrmann, David, primary, Ibrahim, Nuhad K., primary, Morris, Van Karlyle, primary, Kee, Bryan K., primary, Halperin, Daniel M., primary, Nogueras-Gonzalez, Graciela M., primary, Kebriaei, Partow, primary, Shpall, Elizabeth J., primary, Vining, David, primary, Hwu, Patrick, primary, Singh, Harpreet, primary, Reinhardt, Carsten, primary, Britten, Cedrik M., primary, Hilf, Norbert, primary, Weinschenk, Toni, primary, Maurer, Dominik, primary, and Walter, Steffen, primary

Published
2023
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13. Supplemental Figure 5 from Feasibility and Safety of Personalized, Multi-Target, Adoptive Cell Therapy (IMA101): First-in-Human Clinical Trial in Patients with Advanced Metastatic Cancer

Author

Tsimberidou, Apostolia M., primary, Guenther, Kerstin, primary, Andersson, Borje S., primary, Mendrzyk, Regina, primary, Alpert, Amir, primary, Wagner, Claudia, primary, Nowak, Anna, primary, Aslan, Katrin, primary, Satelli, Arun, primary, Richter, Fabian, primary, Kuttruff-Coqui, Sabrina, primary, Schoor, Oliver, primary, Fritsche, Jens, primary, Coughlin, Zoe, primary, Mohamed, Ali S., primary, Sieger, Kerry, primary, Norris, Becky, primary, Ort, Rita, primary, Beck, Jennifer, primary, Vo, Henry Hiep, primary, Hoffgaard, Franziska, primary, Ruh, Manuel, primary, Backert, Linus, primary, Wistuba, Ignacio I., primary, Fuhrmann, David, primary, Ibrahim, Nuhad K., primary, Morris, Van Karlyle, primary, Kee, Bryan K., primary, Halperin, Daniel M., primary, Nogueras-Gonzalez, Graciela M., primary, Kebriaei, Partow, primary, Shpall, Elizabeth J., primary, Vining, David, primary, Hwu, Patrick, primary, Singh, Harpreet, primary, Reinhardt, Carsten, primary, Britten, Cedrik M., primary, Hilf, Norbert, primary, Weinschenk, Toni, primary, Maurer, Dominik, primary, and Walter, Steffen, primary

Published
2023
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14. Supplemental Figure 2 from Feasibility and Safety of Personalized, Multi-Target, Adoptive Cell Therapy (IMA101): First-in-Human Clinical Trial in Patients with Advanced Metastatic Cancer

Author

Tsimberidou, Apostolia M., primary, Guenther, Kerstin, primary, Andersson, Borje S., primary, Mendrzyk, Regina, primary, Alpert, Amir, primary, Wagner, Claudia, primary, Nowak, Anna, primary, Aslan, Katrin, primary, Satelli, Arun, primary, Richter, Fabian, primary, Kuttruff-Coqui, Sabrina, primary, Schoor, Oliver, primary, Fritsche, Jens, primary, Coughlin, Zoe, primary, Mohamed, Ali S., primary, Sieger, Kerry, primary, Norris, Becky, primary, Ort, Rita, primary, Beck, Jennifer, primary, Vo, Henry Hiep, primary, Hoffgaard, Franziska, primary, Ruh, Manuel, primary, Backert, Linus, primary, Wistuba, Ignacio I., primary, Fuhrmann, David, primary, Ibrahim, Nuhad K., primary, Morris, Van Karlyle, primary, Kee, Bryan K., primary, Halperin, Daniel M., primary, Nogueras-Gonzalez, Graciela M., primary, Kebriaei, Partow, primary, Shpall, Elizabeth J., primary, Vining, David, primary, Hwu, Patrick, primary, Singh, Harpreet, primary, Reinhardt, Carsten, primary, Britten, Cedrik M., primary, Hilf, Norbert, primary, Weinschenk, Toni, primary, Maurer, Dominik, primary, and Walter, Steffen, primary

Published
2023
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15. Supplemental Figure 7 from Feasibility and Safety of Personalized, Multi-Target, Adoptive Cell Therapy (IMA101): First-in-Human Clinical Trial in Patients with Advanced Metastatic Cancer

Author

Tsimberidou, Apostolia M., primary, Guenther, Kerstin, primary, Andersson, Borje S., primary, Mendrzyk, Regina, primary, Alpert, Amir, primary, Wagner, Claudia, primary, Nowak, Anna, primary, Aslan, Katrin, primary, Satelli, Arun, primary, Richter, Fabian, primary, Kuttruff-Coqui, Sabrina, primary, Schoor, Oliver, primary, Fritsche, Jens, primary, Coughlin, Zoe, primary, Mohamed, Ali S., primary, Sieger, Kerry, primary, Norris, Becky, primary, Ort, Rita, primary, Beck, Jennifer, primary, Vo, Henry Hiep, primary, Hoffgaard, Franziska, primary, Ruh, Manuel, primary, Backert, Linus, primary, Wistuba, Ignacio I., primary, Fuhrmann, David, primary, Ibrahim, Nuhad K., primary, Morris, Van Karlyle, primary, Kee, Bryan K., primary, Halperin, Daniel M., primary, Nogueras-Gonzalez, Graciela M., primary, Kebriaei, Partow, primary, Shpall, Elizabeth J., primary, Vining, David, primary, Hwu, Patrick, primary, Singh, Harpreet, primary, Reinhardt, Carsten, primary, Britten, Cedrik M., primary, Hilf, Norbert, primary, Weinschenk, Toni, primary, Maurer, Dominik, primary, and Walter, Steffen, primary

Published
2023
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16. Supplemental Figure 8 from Feasibility and Safety of Personalized, Multi-Target, Adoptive Cell Therapy (IMA101): First-in-Human Clinical Trial in Patients with Advanced Metastatic Cancer

Author

Tsimberidou, Apostolia M., primary, Guenther, Kerstin, primary, Andersson, Borje S., primary, Mendrzyk, Regina, primary, Alpert, Amir, primary, Wagner, Claudia, primary, Nowak, Anna, primary, Aslan, Katrin, primary, Satelli, Arun, primary, Richter, Fabian, primary, Kuttruff-Coqui, Sabrina, primary, Schoor, Oliver, primary, Fritsche, Jens, primary, Coughlin, Zoe, primary, Mohamed, Ali S., primary, Sieger, Kerry, primary, Norris, Becky, primary, Ort, Rita, primary, Beck, Jennifer, primary, Vo, Henry Hiep, primary, Hoffgaard, Franziska, primary, Ruh, Manuel, primary, Backert, Linus, primary, Wistuba, Ignacio I., primary, Fuhrmann, David, primary, Ibrahim, Nuhad K., primary, Morris, Van Karlyle, primary, Kee, Bryan K., primary, Halperin, Daniel M., primary, Nogueras-Gonzalez, Graciela M., primary, Kebriaei, Partow, primary, Shpall, Elizabeth J., primary, Vining, David, primary, Hwu, Patrick, primary, Singh, Harpreet, primary, Reinhardt, Carsten, primary, Britten, Cedrik M., primary, Hilf, Norbert, primary, Weinschenk, Toni, primary, Maurer, Dominik, primary, and Walter, Steffen, primary

Published
2023
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17. Feasibility and Safety of Personalized, Multi-Target, Adoptive Cell Therapy (IMA101): First-in-Human Clinical Trial in Patients with Advanced Metastatic Cancer

Author

Tsimberidou, Apostolia M., primary, Guenther, Kerstin, additional, Andersson, Borje S., additional, Mendrzyk, Regina, additional, Alpert, Amir, additional, Wagner, Claudia, additional, Nowak, Anna, additional, Aslan, Katrin, additional, Satelli, Arun, additional, Richter, Fabian, additional, Kuttruff-Coqui, Sabrina, additional, Schoor, Oliver, additional, Fritsche, Jens, additional, Coughlin, Zoe, additional, Mohamed, Ali S., additional, Sieger, Kerry, additional, Norris, Becky, additional, Ort, Rita, additional, Beck, Jennifer, additional, Vo, Henry Hiep, additional, Hoffgaard, Franziska, additional, Ruh, Manuel, additional, Backert, Linus, additional, Wistuba, Ignacio I., additional, Fuhrmann, David, additional, Ibrahim, Nuhad K., additional, Morris, Van Karlyle, additional, Kee, Bryan K., additional, Halperin, Daniel M., additional, Nogueras-Gonzalez, Graciela M., additional, Kebriaei, Partow, additional, Shpall, Elizabeth J., additional, Vining, David, additional, Hwu, Patrick, additional, Singh, Harpreet, additional, Reinhardt, Carsten, additional, Britten, Cedrik M., additional, Hilf, Norbert, additional, Weinschenk, Toni, additional, Maurer, Dominik, additional, and Walter, Steffen, additional

Published
2023
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18. Additional Tables and Figures from A Cancer Research UK First Time in Human Phase I Trial of IMA950 (Novel Multipeptide Therapeutic Vaccine) in Patients with Newly Diagnosed Glioblastoma

Author

Rampling, Roy, primary, Peoples, Sharon, primary, Mulholland, Paul J., primary, James, Allan, primary, Al-Salihi, Omar, primary, Twelves, Christopher J., primary, McBain, Catherine, primary, Jefferies, Sarah, primary, Jackson, Alan, primary, Stewart, Willie, primary, Lindner, Juha, primary, Kutscher, Sarah, primary, Hilf, Norbert, primary, McGuigan, Lesley, primary, Peters, Jane, primary, Hill, Karen, primary, Schoor, Oliver, primary, Singh-Jasuja, Harpreet, primary, Halford, Sarah E., primary, and Ritchie, James W.A., primary

Published
2023
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19. Publisher Correction: Actively personalized vaccination trial for newly diagnosed glioblastoma

Author

Hilf, Norbert, Kuttruff-Coqui, Sabrina, Frenzel, Katrin, Bukur, Valesca, Stevanović, Stefan, Gouttefangeas, Cecile, Platten, Michael, Tabatabai, Ghazaleh, Dutoit, Valerie, van der Burg, Sjoerd H., Straten, Per thor, Martinez-Ricarte, Francisco, Ponsati, Berta, Okada, Hideho, Lassen, Ulrik, Admon, Arie, Ottensmeier, Christian H., Ulges, Alexander, Kreiter, Sebastian, von Deimling, Andreas, Skardelly, Marco, Migliorini, Denis, Kroep, Judith R., Idorn, Manja, Rodon, Jordi, Piro, Jordi, Poulsen, Hans S., Shraibman, Bracha, McCann, Katy, Mendrzyk, Regina, Lower, Martin, Stieglbauer, Monika, Britten, Cedrik M., Capper, David, Welters, Marij J. P., Sahuquillo, Juan, Kiesel, Katharina, Derhovanessian, Evelyna, Rusch, Elisa, Bunse, Lukas, Song, Colette, Heesch, Sandra, Wagner, Claudia, Kemmer-Bruck, Alexandra, Ludwig, Jorg, Castle, John C., Schoor, Oliver, Tadmor, Arbel D., Green, Edward, Fritsche, Jens, Meyer, Miriam, Pawlowski, Nina, Dorner, Sonja, Hoffgaard, Franziska, Rossler, Bernhard, Maurer, Dominik, Weinschenk, Toni, Reinhardt, Carsten, Huber, Christoph, Rammensee, Hans-Georg, Singh-Jasuja, Harpreet, Sahin, Ugur, Dietrich, Pierre-Yves, and Wick, Wolfgang

Published
2019
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20. 959 Safety and anti-tumor activity of TCR-engineered autologous, PRAME-directed T cells across multiple advanced solid cancers at low doses – clinical update on the ACTengine® IMA203 trial

Author

Wermke, Martin, primary, Tsimberidou, Apostolia-Maria, additional, Mohamed, Ali, additional, Mayer-Mokler, Andrea, additional, Satelli, Arun, additional, Reinhardt, Carsten, additional, Araujo, Dejka, additional, Maurer, Dominik, additional, Blumenschein, George Jr, additional, Singh, Harpreet, additional, Luke, Jason, additional, Guenther, Kerstin, additional, Kalra, Mamta, additional, Chatterjee, Manik, additional, Hilf, Norbert, additional, Mendrzyk, Regina, additional, Walter, Steffen, additional, Eck, Stephen, additional, Holderried, Tobias AW, additional, Weinschenk, Toni, additional, Morris, Van, additional, Alsdorf, Winfried, additional, and Britten, Cedrik M, additional

Published
2021
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21. Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival

Author

Walter, Steffen, Weinschenk, Toni, Stenzl, Arnulf, Zdrojowy, Romuald, Pluzanska, Anna, Szczylik, Cezary, Staehler, Michael, Brugger, Wolfram, Dietrich, Pierre-Yves, Mendrzyk, Regina, Hilf, Norbert, Schoor, Oliver, Fritsche, Jens, Mahr, Andrea, Maurer, Dominik, Vass, Verona, Trautwein, Claudia, Lewandrowski, Peter, Flohr, Christian, Pohla, Heike, Stanczak, Janusz J., Bronte, Vincenzo, Mandruzzato, Susanna, Biedermann, Tilo, Pawelec, Graham, Derhovanessian, Evelyna, Yamagishi, Hisakazu, Miki, Tsuneharu, Hongo, Fumiya, Takaha, Natsuki, Hirakawa, Kosei, Tanaka, Hiroaki, Stevanovic, Stefan, Frisch, Jurgen, Mayer-Mokler, Andrea, Kirner, Alexandra, Rammensee, Hans-Georg, Reinhardt, Carsten, and Singh-Jasuja, Harpreet

Subjects
Research, Dosage and administration, Health aspects, Cancer vaccines -- Dosage and administration, Cyclophosphamide -- Dosage and administration, Polypeptides -- Health aspects, Immune response -- Research
Abstract

Therapeutic cancer vaccines hold the promise of combining meaningful efficacy (prolongation of survival) with very good safety and tolerability, as has been shown in several recent randomized trials. (1-3) However, [...], IMA901 is the first therapeutic vaccine for renal cell cancer (RCC) consisting of multiple tumor-associated peptides (TUMAPs) confirmed to be naturally presented in human cancer tissue. We treated a total of 96 human leukocyte antigen A (HLA-A)*02+ subjects with advanced RCC with IMA901 in two consecutive studies. In the phase 1 study, the T cell responses of the patients to multiple TUMAPs were associated with better disease control and lower numbers of prevaccine forkhead box P3 (FOXP3)+ regulatory T ([T.sub.reg]) cells. The randomized phase 2 trial showed that a single dose of cyclophosphamide reduced the number of [T.sub.reg] cells and confirmed that immune responses to multiple TUMAPs were associated with longer overall survival. Furthermore, among six predefined populations of myeloid-derived suppressor cells, two were prognostic for overall survival, and among over 300 serum biomarkers, we identified apolipoprotein A-I (APOA1) and chemokine (C-C motif) ligand 17 (CCL17) as being predictive for both immune response to IMA901 and overall survival. A randomized phase 3 study to determine the clinical benefit of treatment with IMA901 is ongoing.

Published
2012
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23. Exploiting the glioblastoma peptidome to discover novel tumour-associated antigens for immunotherapy

Author

Dutoit, Valérie, Herold-Mende, Christel, Hilf, Norbert, Schoor, Oliver, Beckhove, Philipp, Bucher, Judith, Dorsch, Katharina, Flohr, Sylvia, Fritsche, Jens, Lewandrowski, Peter, Lohr, Jennifer, Rammensee, Hans-Georg, Stevanovic, Stefan, Trautwein, Claudia, Vass, Verona, Walter, Steffen, Walker, Paul R., Weinschenk, Toni, Singh-Jasuja, Harpreet, and Dietrich, Pierre-Yves

Published
2012
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24. 293 Resultsof the first-in-human clinical trial with personalized multi-target adoptive cell therapy (ACTolog IMA101)

Author

Tsimberidou, Apostolia, primary, Guenther, Kerstin, additional, Alpert, Amir, additional, Andersson, Borje, additional, Coughlin, Zoe, additional, Fritsche, Jens, additional, Hilf, Norbert, additional, Hwu, Patrick, additional, Kalra, Mamta, additional, Kuttruff-Coqui, Sabrina, additional, Maurer, Dominik, additional, Mendrzyk, Regina, additional, Mohamed, Ali, additional, Norris, Becky, additional, Nowak, Anna, additional, Ort, Rita, additional, Reinhardt, Carsten, additional, Richter, Fabian, additional, Satelli, Arun, additional, Schoor, Oliver, additional, Sieger, Kerry, additional, Singh, Harpreet, additional, Vining, David, additional, Wagner, Claudia, additional, Weinschenk, Toni, additional, Yee, Cassian, additional, and Walter, Steffen, additional

Published
2020
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25. Identification of Tumor Antigens Among the HLA Peptidomes of Glioblastoma Tumors and Plasma

Author

Shraibman, Bracha, Barnea, Eilon, Kadosh, Dganit Melamed, Haimovich, Yael, Slobodin, Gleb, Rosner, Itzhak, López-Larrea, Carlos, Hilf, Norbert, Kuttruff, Sabrina, Song, Colette, Britten, Cedrik, Castle, John, Kreiter, Sebastian, Frenzel, Katrin, Tatagiba, Marcos, Tabatabai, Ghazaleh, Dietrich, Pierre-Yves, Dutoit, Valérie, Wick, Wolfgang, Platten, Michael, Winkler, Frank, von Deimling, Andreas, Kroep, Judith, Sahuquillo, Juan, Martinez-Ricarte, Francisco, Rodon, Jordi, Lassen, Ulrik, Ottensmeier, Christian, van der Burg, Sjoerd H., Thor Straten, Per, Poulsen, Hans Skovgaard, Ponsati, Berta, Okada, Hideho, Rammensee, Hans-Georg, Sahin, Ugur, Singh, Harpreet, and Admon, Arie

Published
2018
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28. Withdrawal: Identification of tumor antigens among the HLA peptidomes of glioblastoma tumors and plasma.

Author

Shraibman, Bracha, primary, Barnea, Eilon, additional, Kadosh, Dganit Melamed, additional, Haimovich, Yael, additional, Slobodin, Gleb, additional, Rosner, Itzhak, additional, López-Larrea, Carlos, additional, Hilf, Norbert, additional, Kuttruff, Sabrina, additional, Song, Colette, additional, Britten, Cedrik, additional, Castle, John, additional, Kreiter, Sebastian, additional, Frenzel, Katrin, additional, Tatagiba, Marcos, additional, Tabatabai, Ghazaleh, additional, Dietrich, Pierre-Yves, additional, Dutoit, Valérie, additional, Wick, Wolfgang, additional, Platten, Michael, additional, Winkler, Frank, additional, von Deimling, Andreas, additional, Kroep, Judith, additional, Sahuquillo, Juan, additional, Martinez-Ricarte, Francisco, additional, Rodon, Jordi, additional, Lassen, Ulrik, additional, Ottensmeier, Christian, additional, van der Burg, Sjoerd H., additional, Thor Straten, Per, additional, Poulsen, Hans Skovgaard, additional, Ponsati, Berta, additional, Okada, Hideho, additional, Rammensee, Hans-Georg, additional, Sahin, Ugur, additional, Singh, Harpreet, additional, and Admon, Arie, additional

Published
2019
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31. Identification of Tumor Antigens Among the HLA Peptidomes of Glioblastoma Tumors and Plasma

Author

Shraibman, Bracha, Barnea, Eilon, Kadosh, Dganit Melamed, Haimovich, Yael, Slobodin, Gleb, Rosner, Itzhak, López-Larrea, Carlos, Hilf, Norbert, Kuttruff, Sabrina, Song, Colette, Britten, Cedrik, Castle, John, Kreiter, Sebastian, Frenzel, Katrin, Tatagiba, Marcos, Tabatabai, Ghazaleh, Dietrich, Pierre-Yves, Dutoit, Valérie, Wick, Wolfgang, Platten, Michael, Winkler, Frank, von Deimling, Andreas, Kroep, Judith, Sahuquillo, Juan, Martinez-Ricarte, Francisco, Rodon, Jordi, Lassen, Ulrik, Ottensmeier, Christian, van der Burg, Sjoerd H, Thor Straten, Per, Poulsen, Hans Skovgaard, Ponsati, Berta, Okada, Hideho, Rammensee, Hans-Georg, Sahin, Ugur, Singh, Harpreet, Admon, Arie, Shraibman, Bracha, Barnea, Eilon, Kadosh, Dganit Melamed, Haimovich, Yael, Slobodin, Gleb, Rosner, Itzhak, López-Larrea, Carlos, Hilf, Norbert, Kuttruff, Sabrina, Song, Colette, Britten, Cedrik, Castle, John, Kreiter, Sebastian, Frenzel, Katrin, Tatagiba, Marcos, Tabatabai, Ghazaleh, Dietrich, Pierre-Yves, Dutoit, Valérie, Wick, Wolfgang, Platten, Michael, Winkler, Frank, von Deimling, Andreas, Kroep, Judith, Sahuquillo, Juan, Martinez-Ricarte, Francisco, Rodon, Jordi, Lassen, Ulrik, Ottensmeier, Christian, van der Burg, Sjoerd H, Thor Straten, Per, Poulsen, Hans Skovgaard, Ponsati, Berta, Okada, Hideho, Rammensee, Hans-Georg, Sahin, Ugur, Singh, Harpreet, and Admon, Arie

Abstract

Glioblastoma multiforme (GBM) is the most aggressive brain tumor with poor prognosis to most patients. Immunotherapy of GBM is a potentially beneficial treatment option, whose optimal implementation may depend on familiarity with tumor specific antigens, presented as HLA peptides by the GBM cells. Furthermore, early detection of GBM, such as by a routine blood test, may improve survival, even with the current treatment modalities. This study includes large-scale analyses of the HLA peptidome (immunopeptidome) of the plasma-soluble HLA molecules (sHLA) of 142 plasma samples, and the membranal HLA of GBM tumors of 10 of these patients' tumor samples. Tumor samples were fresh-frozen immediately after surgery and the plasma samples were collected before, and at multiple visits after surgery. In total, this HLA peptidome analysis involved 52 different HLA allotypes and resulted in the identification of more than 35,000 different HLA peptides. Strong correlations were observed in the signal intensities and in the repertoires of identified peptides between the tumors and plasma-soluble HLA peptidomes of the individual patients, whereas low correlations were observed between these HLA peptidomes and the tumors' proteomes. HLA peptides derived from Cancer/Testis Antigens (CTAs) were selected based on their presence among the HLA peptidomes of the patients and absence of expression of their source genes from any healthy and essential human tissues, except from immune-privileged sites. Additionally, peptides were selected as potential biomarkers if their levels in the plasma-sHLA peptidome were significantly reduced after the removal of tumor mass. The CTAs identified among the analyzed HLA peptidomes provide new opportunities for personalized immunotherapy and for early diagnosis of GBM.

Published
2019

32. Abstract A020: Immunomonitoring for actively personalized peptide vaccines (APVACs) during immunotherapeutic treatment of glioblastoma

Author

Ulges, Alexander, primary, Hilf, Norbert, additional, Wick, Wolfgang, additional, Platten, Michael, additional, Dietrich, Pierre-Yves, additional, Frenzel, Katrin, additional, Admon, Arie, additional, Burg, Sjoerd S.H. van der, additional, Deimling, Andreas von, additional, Straten, Per thor, additional, Gouttefangeas, Cecile, additional, Kroep, Judith R., additional, Martínez-Ricarte, Francisco, additional, Okada, Hideo, additional, Ottensmeier, Christian H., additional, Ponsati, Berta, additional, Poulsen, Hans S., additional, Stevanovic, Stefan, additional, Tabatabai, Ghazaleh, additional, Rammensee, Hans-Georg, additional, Sahin, Ugur, additional, Maurer, Dominik, additional, and Mendrzyk, Regina, additional

Published
2019
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33. Actively personalized vaccination trial for newly diagnosed glioblastoma

Author

Hilf, Norbert, primary, Kuttruff-Coqui, Sabrina, additional, Frenzel, Katrin, additional, Bukur, Valesca, additional, Stevanović, Stefan, additional, Gouttefangeas, Cécile, additional, Platten, Michael, additional, Tabatabai, Ghazaleh, additional, Dutoit, Valerie, additional, van der Burg, Sjoerd H., additional, thor Straten, Per, additional, Martínez-Ricarte, Francisco, additional, Ponsati, Berta, additional, Okada, Hideho, additional, Lassen, Ulrik, additional, Admon, Arie, additional, Ottensmeier, Christian H., additional, Ulges, Alexander, additional, Kreiter, Sebastian, additional, von Deimling, Andreas, additional, Skardelly, Marco, additional, Migliorini, Denis, additional, Kroep, Judith R., additional, Idorn, Manja, additional, Rodon, Jordi, additional, Piró, Jordi, additional, Poulsen, Hans S., additional, Shraibman, Bracha, additional, McCann, Katy, additional, Mendrzyk, Regina, additional, Löwer, Martin, additional, Stieglbauer, Monika, additional, Britten, Cedrik M., additional, Capper, David, additional, Welters, Marij J. P., additional, Sahuquillo, Juan, additional, Kiesel, Katharina, additional, Derhovanessian, Evelyna, additional, Rusch, Elisa, additional, Bunse, Lukas, additional, Song, Colette, additional, Heesch, Sandra, additional, Wagner, Claudia, additional, Kemmer-Brück, Alexandra, additional, Ludwig, Jörg, additional, Castle, John C., additional, Schoor, Oliver, additional, Tadmor, Arbel D., additional, Green, Edward, additional, Fritsche, Jens, additional, Meyer, Miriam, additional, Pawlowski, Nina, additional, Dorner, Sonja, additional, Hoffgaard, Franziska, additional, Rössler, Bernhard, additional, Maurer, Dominik, additional, Weinschenk, Toni, additional, Reinhardt, Carsten, additional, Huber, Christoph, additional, Rammensee, Hans-Georg, additional, Singh-Jasuja, Harpreet, additional, Sahin, Ugur, additional, Dietrich, Pierre-Yves, additional, and Wick, Wolfgang, additional

Published
2018
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34. ATIM-20. GAPVAC-101 TRIAL OF A HIGHLY PERSONALIZED PEPTIDE VACCINATION FOR PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

Author

Wick, Wolfgang, primary, Dietrich, Pierre-Yves, additional, HIlf, Norbert, additional, Platten, Michael, additional, Frenzel, Katrin, additional, Admon, Arie, additional, van der Burg, Sjoerd, additional, von Deimling, Andreas, additional, Gouttefangeas, Cecile, additional, Kroep, Judith, additional, Martinez-Ricarte, Francisco, additional, Okada, Hideho, additional, Ottensmeier, Christian, additional, Ponsati, Berta, additional, Poulsen, Hans, additional, Stevanovic, Stefan, additional, Tabatabai, Ghazaleh, additional, Rammensee, Hans-Georg, additional, Sahin, Ugur, additional, and Singh-Jasuja, Harpreet, additional

Published
2018
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35. Abstract 662: IMA_Detect: Mass spectrometry guided development and clinical application of a companion diagnostic for adoptive cellular therapy against tumor associated HLA peptides

Author

Fritsche, Jens, primary, Satelli, Arun, additional, Hörzer, Helen, additional, Rakitsch, Barbara, additional, Hoffgaard, Franziska, additional, Hilf, Norbert, additional, Schoor, Oliver, additional, Singh-Jasuja, Harpreet, additional, and Toni, Weinschenk, additional

Published
2018
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36. Abstract CT127: Phase I adoptive cellular therapy trial with actively personalized, multi-targeted CD8+ T-cells in patients with relapsed and/or refractory solid cancers (ACTologIMA101-101)

Author

Ma, Hong, primary, Kuttruff, Sabrina, additional, Stewart, Chad, additional, Bulliard, Yannick, additional, Stephens, Geoffrey, additional, Schoor, Oliver, additional, Satelli, Arun, additional, Hilf, Norbert, additional, Sieger, Kerry, additional, Fritsche, Jens, additional, Maurer, Dominik, additional, Mohamed, Ali, additional, Weinschenk, Toni, additional, Reinhardt, Carsten, additional, Walter, Steffen, additional, Singh, Harpreet, additional, Hwu, Patrick, additional, Yee, Cassian, additional, Andersson, Borje, additional, and Tsimberidou, Apostolia-Marie, additional

Published
2018
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37. A Cancer Research UK first time in human phase I trial of IMA950 (novel multi peptide therapeutic vaccine) in patients with newly diagnosed glioblastoma

Author

Rampling, Roy, Peoples, Sharon, Mulholland, Paul J., James, Allan, Al-Salihi, Omar, Twelves, Christopher J., McBain, Catherine, Jefferies, Sarah, Jackson, Alan, Stewart, Willie, Lindner, Juha, Kutscher, Sarah, Hilf, Norbert, McGuigan, Lesley, Peters, Jane, Hill, Karen, Schoor, Oliver, Singh-Jasuja, Harpreet, Halford, Sarah E., and Ritchie, James W.A.

Abstract

PURPOSE: To perform a two-cohort, phase 1 safety and immunogenicity study of IMA950 in addition to standard chemo-radiotherapy (CRT) and adjuvant temozolomide in patients with newly diagnosed glioblastoma (GBM). IMA950 is a novel GBM specific therapeutic vaccine containing 11 tumor-associated peptides (TUMAPs), identified on human leukocyte antigen (HLA) surface receptors in primary human GBM tissue. EXPERIMENTAL DESIGN: Patients were HLA A*02 positive and had undergone tumor resection. Vaccination comprised 11 intradermal injections with IMA950 plus GM-CSF over a 24 week period, beginning 7-14 days prior to initiation of CRT (Cohort 1) or 7 days post CRT (Cohort 2). Safety was assessed according to NCI CTCAE Version 4.0 and TUMAP specific T cell immune responses determined. Secondary observations included progression-free survival (PFS), pre-treatment regulatory T-cell (Treg) levels and the effect of steroids on T-cell responses. RESULTS: Forty five patients were recruited. Related adverse events included minor injection site reactions, rash, pruritus, fatigue, neutropenia and single cases of allergic reaction, anemia and anaphylaxis. Two patients experienced Grade 3 dose limiting toxicity of fatigue and anaphylaxis. Of 40 evaluable patients, 36 were TUMAP responders and 20 were multi-TUMAP responders, with no important differences between cohorts. No effect of pre-treatment Treg levels on IMA950 immunogenicity was observed and steroids did not affect TUMAP responses. PFS was 74% at 6 months and 31% at 9 months. CONCLUSION: IMA950 plus GM-CSF was well tolerated with the primary immunogenicity endpoint of observing multi-TUMAP responses in at least 30% of patients exceeded. Further development of IMA950 is encouraged.

Published
2016

38. IMMU-52. SELECTION OF GLIOMA T-CELL THERAPY TARGETS BASED ON THE ANALYSIS OF TUMOR IMMUNOPEPTIDOME AND EXPRESSION PROFILES

Author

Carrera, Diego, primary, Hayes, Josie, additional, Mueller, Soeren, additional, Shelton, Samuel J, additional, Weinschenk, Toni, additional, Song, Colette, additional, Fritsche, Jens, additional, Schoor, Oliver, additional, Kuttruff-Coqui, Sabrina, additional, Hilf, Norbert, additional, Kohanbash, Gary, additional, Watchmaker, Payal, additional, Oldham, Michael C, additional, Costello, Joseph, additional, Singh, Harpreet, additional, and Okada, Hideho, additional

Published
2017
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39. Abstract 3753: Identification of antibodies against a novel tumor-associated MHC/peptide-target and generation of highly specific and potent HLA-A*02MMP1-003/CD3 TandAbs

Author

Weinschenk, Toni, primary, Rajkovic, Erich, additional, Reusch, Uwe, additional, Weichel, Michael, additional, Ellwanger, Kristina, additional, Fucek, Ivica, additional, Tesar, Michael, additional, Hinz, Dominik, additional, Molkenthin, Vera, additional, Bunk, Sebastian, additional, Hilf, Norbert, additional, Schoor, Oliver, additional, Maurer, Dominik, additional, Mock, Kerstin, additional, Reinhardt, Carsten, additional, and Treder, Martin, additional

Published
2017
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40. Exploiting the glioblastoma peptidome to discover novel tumour-associated antigens for immunotherapy

Author

Dutoit, Valérie, Herold-Mende, Christel, Hilf, Norbert, Schoor, Oliver, Beckhove, Philipp, Bucher, Judith, Dorsch, Katharina, Flohr, Sylvia, Fritsche, Jens, Lewandrowski, Peter, Lohr, Jennifer, Rammensee, Hans-Georg, Stevanovic, Stefan, Trautwein, Claudia, Vass, Verona, Walter, Steffen, Walker, Paul R., Weinschenk, Toni, Singh-Jasuja, Harpreet, Dietrich, Pierre-Yves, Dutoit, Valérie, Herold-Mende, Christel, Hilf, Norbert, Schoor, Oliver, Beckhove, Philipp, Bucher, Judith, Dorsch, Katharina, Flohr, Sylvia, Fritsche, Jens, Lewandrowski, Peter, Lohr, Jennifer, Rammensee, Hans-Georg, Stevanovic, Stefan, Trautwein, Claudia, Vass, Verona, Walter, Steffen, Walker, Paul R., Weinschenk, Toni, Singh-Jasuja, Harpreet, and Dietrich, Pierre-Yves

Abstract

Peptides presented at the cell surface reflect the protein content of the cell; those on HLA class I molecules comprise the critical peptidome elements interacting with CD8 T lymphocytes. We hypothesize that peptidomes from ex vivo tumour samples encompass immunogenic tumour antigens. Here, we uncover >6000 HLA-bound peptides from HLA-A*02+ glioblastoma, of which over 3000 were restricted by HLA-A*02. We prioritized in-depth investigation of 10 glioblastoma-associated antigens based on high expression in tumours, very low or absent expression in healthy tissues, implication in gliomagenesis and immunogenicity. Patients with glioblastoma showed no T cell tolerance to these peptides. Moreover, we demonstrated specific lysis of tumour cells by patients' CD8+ T cells in vitro. In vivo, glioblastoma-specific CD8+ T cells were present at the tumour site. Overall, our data show the physiological relevance of the peptidome approach and provide a critical advance for designing a rational glioblastoma immunotherapy. The peptides identified in our study are currently being tested as a multipeptide vaccine (IMA950) in patients with glioblastoma

Published
2017

41. A Cancer Research UK First Time in Human Phase I Trial of IMA950 (Novel Multipeptide Therapeutic Vaccine) in Patients with Newly Diagnosed Glioblastoma

Author

Rampling, Roy, primary, Peoples, Sharon, additional, Mulholland, Paul J., additional, James, Allan, additional, Al-Salihi, Omar, additional, Twelves, Christopher J., additional, McBain, Catherine, additional, Jefferies, Sarah, additional, Jackson, Alan, additional, Stewart, Willie, additional, Lindner, Juha, additional, Kutscher, Sarah, additional, Hilf, Norbert, additional, McGuigan, Lesley, additional, Peters, Jane, additional, Hill, Karen, additional, Schoor, Oliver, additional, Singh-Jasuja, Harpreet, additional, Halford, Sarah E., additional, and Ritchie, James W.A., additional

Published
2016
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42. Abstract 2654: GAPVAC-101 phase I trial: First data of an innovative actively personalized peptide vaccination trial in patients with newly diagnosed glioblastoma

Author

Hilf, Norbert, primary, Frenzel, Katrin, additional, Kuttruff-Coqui, Sabrina, additional, Heesch, Sandra, additional, Kreiter, Sebastian, additional, Admon, Arie, additional, Bukur, Valesca, additional, van der Burg, Sjoerd, additional, Gouttefangeas, Cecile, additional, Kroep, Judith R., additional, Schoenmaekers-Welters, Marij, additional, Piro, Jordi, additional, Ponsati, Berta, additional, Poulsen, Hans Skovgaard, additional, Lassen, Ulrik, additional, Martinez-Ricarte, Francisco, additional, Rodon, Jordi, additional, Sahuquillo, Juan, additional, Stieglbauer, Monika, additional, Stevanovic, Stefan, additional, thor Straten, Per, additional, Skardelly, Marco, additional, Tabatabai, Ghazaleh, additional, Platten, Michael, additional, Capper, David, additional, von Deimling, Andreas, additional, Dutoit, Valérie, additional, Okada, Hideho, additional, Ottensmeier, Christian, additional, Feist, Randi Kristina, additional, Fritsche, Jens, additional, Laske, Karoline, additional, Lewandrowski, Peter, additional, Löwer, Martin, additional, Mendryzk, Regina, additional, Meyer, Miriam, additional, Reinhardt, Carsten, additional, Rössler, Bernhard, additional, Paruzynski, Anna, additional, Pawlowski, Nina, additional, Song, Colette, additional, Lea, Stevermann, additional, Weinschenk, Toni, additional, Huber, Christoph, additional, Rammensee, Hans-Georg, additional, Dietrich, Pierre-Yves, additional, Wolfgang, Wick, additional, Sahin, Ugur, additional, and Singh-Jasuja, Harpreet, additional

Published
2016
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43. Mehr als ein Alarmsignal - Die vielfältigen Rollen des Hitzeschockproteins Gp96 in der angeborenen und erworbenen Immunität

Author

Hilf, Norbert and Rammensee, Hans-Georg

Subjects
endocytosis, Toll-like receptor , antigen presenting cell , cytotoxic T cell , platelets, Hitzeschock-Proteine , Immunsystem , Dendritische Zelle , Thrombozyt , Killerzelle , T-Lymphozyt , Endocytose, Toll-like Rezeptor , Antigen-präsentierende Zelle , Gp96
Abstract

Immunization with tumor lysates induces tumor protection against the original tumor in mouse models. Surprisingly, all tumor antigens purified from the lysates belong to the heat shock protein (HSP) family and are not mutated compared to the proteins in normal tissue. Instead, their immunogenicity is based on tumor-specific peptides bound to the HSPs. The investigation of the mechanisms that allow the induction of efficient immune responses with low doses of HSP:peptide complexes was the focus of this work, which was performed using mainly the ER-resident HSP Gp96. We were able to show (chapter 3) that HSP-mediated immunity depends on its receptor-mediated uptake by professional antigen presenting cells (APCs). This is a prerequisite for the efficient shuttling of the associated peptides to the MHC molecules of the APC. Moreover, specific immune responses require the unspecific activation of APCs by danger signals. These lead to the upregulation of costimulatory molecules and the secretion of pro-inflammatory cytokines. Danger signals can be pathogen-derived as well as endogenous substances. Here we provide evidence that Gp96 itself is a danger signal (chapter 4). Gp96 triggers APC activation via the Toll-like receptors (TLRs) 4 and 2 pathways which are also used by pathogen-derived danger signals (chapter 6). TLR-mediated activation of the immune system is of importance for the specific immune response (chapter 7). Priming of cytotoxic T-lymphocytes (CTLs) after a viral challenge depends on either CD4+ T cells or TLR-mediated signals. If both are missing, CTL priming is impaired. For minor H specific CTL responses, TLR signaling is strictly required. A similar importance of TLR-mediated signals can be expected for Gp96-induced immune responses. The strong inflammatory signals triggered by Gp96 have to be controlled in vivo. In chapter 5, it is shown that human platelets are able to control the immunostimulatory capacities of Gp96. Platelets bind high amounts of Gp96, especially after their activation by thrombin. Thereby, free Gp96 is withdrawn resulting in a lower APC activation. This mechanism might have a physiological role during wound healing to prevent the adverse effects of chronic inflammation. HSPs are more than endogenous danger signals released from dying cells. They also deliver detailed information about the events that caused the death. They combine everything in a single protein that is required for the induction of an efficient and specific immune response. Die Injektion von Tumorlysaten bewirkt im Mausmodell eine protektive Immunität gegen den verwendeten Tumor. Alle in den Arbeiten von P. Srivastava identifizierten Tumorantigene gehören jedoch zur Familie der Hitzeschockproteine (HSPs) und sind nicht gegenüber dem Protein im Ursprungsgewebe verändert. Die Immunogenität rührt vielmehr von an das HSP gebundenen, tumorspezifischen Peptiden. Die Aufklärung der Mechanismen, die die Induktion von Immunantworten mit geringsten Dosen von HSP-Peptid Komplexen ermöglichen, stand im Mittelpunkt dieser Arbeit, die vorwiegend mit dem ER-ständigen HSP Gp96 durchgeführt wurde. Es konnte gezeigt werden, dass eine Voraussetzung HSP-vermittelter Immunität dessen Rezeptor-vermittelte Endozytose ist (Kapitel 3). Diese ist grundlegend für die effektive Repräsentierung der assoziierten Proteine in den MHC-Molekülen der APCs. Eine spezifische Immunantwort bedarf darüber hinaus auch unspezifischer Alarmsignale, die unter anderem die verstärkte Expression von costimulatorischen Molekülen auf professionellen Antigen-präsentierenden Zellen (APCs) bewirken. Diese Alarmsignale können Pathogen-assoziierte Signaturen oder endogene Substanzen sein. Wir konnten zeigen, dass Gp96 selbst ein solches Alarmsignal ist (Kapitel 4). Dabei vermitteln die Toll-like Rezeptoren (TLR) 4 und 2 die Gp96-induzierte Aktivierung (Kapitel 6), die auch Rezeptoren für Pathogen-assoziierte Alarmsignale sind. TLR-vermittelte Aktivierung des Immunsystems ist in anderen Systemen von Bedeutung für die spezifische Immunantwort (Kapitel 7): Für die Aktivierung cytotoxischer T-Zellen (CTLs) nach einer Virusinfektion sind entweder CD4+ T-Helferzellen oder TLR-Signalwege nötig. In Abwesenheit beider Signalwege findet kein derartiges „Priming“ von CTLs statt. Für das CTL-Priming gegen Minorhistokompatibilitätsantigene sind TLR-Signale sogar unabdingbar. Eine ähnliche Bedeutung der TLR-Signalwege kann für Gp96 erwartet werden. Die von Gp96 ausgelöste Entzündungreaktion muss in vivo begrenzt werden. In Kapitel 5 wird ein solcher Kontrollmechanismus durch Thrombozyten beschrieben, die besonders nach ihrer Aktivierung Gp96 sehr gut binden und die Aktivierung von APCs unterbinden. HSPs sind mehr als nur Alarmsignale, die aus sterbenden Zellen freigesetzt das Immunsystem unspezifisch aktivieren. Sie liefern zusätzlich Informationen über den Grund, der zum Tod ihrer Ursprungszelle führte, und ermöglichen so eine effiziente Immunantwort.

Published
2003

45. Abstract SY27-03: Biomarker-guided development of novel multi-peptide cancer vaccines - from discovery to phase lll trials.

Author

Singh-Jasuja, Harpreet, primary, Walter, Steffen, additional, Weinschenk, Toni, additional, Kirner, Alexandra, additional, Mayer-Mokler, Andrea, additional, Hilf, Norbert, additional, Schoor, Oliver, additional, Dietrich, Pierre-Yves, additional, Richtie, James, additional, Rampling, Roy, additional, Mayer, Frank, additional, Stenzl, Arnulf, additional, Rini, Brian, additional, Reinhardt, Carsten, additional, and Rammensee, Hans-Georg, additional

Published
2013
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46. Overall survival (OS) of advanced colorectal cancer (aCRC) patients (pts) treated with the multipeptide vaccine IMA910: Results of a matched-pair analysis with arm C pts from COIN.

Author

Maughan, Tim, primary, Adams, Richard A., additional, Mayer-Mokler, Andrea, additional, Nowara, Elzbieta, additional, Torday, Laszlo, additional, Cseh, Jozsef, additional, Hoehler, Thomas, additional, Hitre, Erika, additional, Folprecht, Gunnar, additional, Fisher, David, additional, Ludwig, Joerg, additional, Roessler, Bernhard, additional, Kuttruff, Sabrina, additional, Walter, Steffen, additional, Hilf, Norbert, additional, Schoor, Oliver, additional, Weinschenk, Toni, additional, Singh, Harpreet, additional, Reinhardt, Carsten, additional, and Mayer, Frank, additional

Published
2012
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47. Abstract 5365: Prolonged survival of patients with advanced renal cancer responding to multi-peptide vaccine IMA901 after single-dose cyclophosphamide

Author

Walter, Steffen, primary, Weinschenk, Toni, additional, Stenzl, Arnulf, additional, Zdrojowy, Romuald, additional, Pluzanska, Anna, additional, Szczylik, Cezary, additional, Staehler, Michael, additional, Brugger, Wolfram, additional, Dietrich, Pierre-Yves, additional, Hilf, Norbert, additional, Schoor, Oliver, additional, Fritsche, Jens, additional, Mahr, Andrea, additional, Mendrzyk, Regina, additional, Maurer, Dominik, additional, Vass, Verona, additional, Trautwein, Claudia, additional, Lewandrowski, Peter, additional, Flohr, Christian, additional, Pohla, Heike, additional, Stanczak, Janusz J., additional, Bronte, Vincenzo, additional, Mandruzzato, Susanna, additional, Biedermann, Tilo, additional, Pawelec, Graham, additional, Derhovanessian, Evelyna, additional, Yamagishi, Hisakazu, additional, Miki, Tsuneharu, additional, Hongo, Fumiya, additional, Takaha, Natsuki, additional, Hirakawa, Kosei, additional, Tanaka, Hiroaki, additional, Stevanovic, Stefan, additional, Rammensee, Hans-Georg, additional, Frisch, Jürgen, additional, Mayer-Mokler, Andrea, additional, Kirner, Alexandra, additional, Finke, James, additional, Rini, Brian, additional, Reinhardt, Carsten, additional, and Singh, Harpreet, additional

Published
2012
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48. Abstract 302: Multiple distinct populations of myeloid derived suppressor cells in IMA901 treated renal cell cancer patients correlate with survival and with T-cell dysfunctions

Author

Walter, Steffen, primary, Hilf, Norbert, additional, Mendrzyk, Regina, additional, Maurer, Dominik, additional, Weinschenk, Toni, additional, Kirner, Alexandra, additional, Bronte, Vincenzo, additional, Mandruzzato, Susanna, additional, Stenzl, Arnulf, additional, Reinhardt, Carsten, additional, and Singh, Harpreet, additional

Published
2011
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