14 results on '"Andersen, Mads Hald"'
Search Results
2. The T-win® technology: immune-modulating vaccines
- Author
-
Andersen, Mads Hald
- Published
- 2019
- Full Text
- View/download PDF
3. Anti-regulatory T cells
- Author
-
Andersen, Mads Hald
- Published
- 2017
- Full Text
- View/download PDF
4. PD-L1-specific T cells
- Author
-
Ahmad, Shamaila Munir, Borch, Troels Holz, Hansen, Morten, and Andersen, Mads Hald
- Published
- 2016
- Full Text
- View/download PDF
5. Potential roles of self-reactive T cells in autoimmunity: lessons from cancer immunology
- Author
-
Andersen, Mads Hald
- Published
- 2014
- Full Text
- View/download PDF
6. Self-reactive T cells: suppressing the suppressors
- Author
-
Becker, Jürgen C., thor Straten, Per, and Andersen, Mads Hald
- Published
- 2014
- Full Text
- View/download PDF
7. Anti-PD-L1/PD-L2 therapeutic vaccination in untreated chronic lymphocytic leukemia patients with unmutated IgHV.
- Author
-
Klausen, Uffe, Grauslund, Jacob Handlos, Dahlager Jørgensen, Nicolai Grønne, Ahmad, Shamaila Munir, Jonassen, Merete, Weis-Banke, Stine Emilie, Martinenaite, Evelina, Pedersen, Lone Bredo, Lisle, Thomas Landkildehus, Gang, Anne Ortved, Enggaard, Lisbeth, Hansen, Morten, Holmström, Morten Orebo, Met, Özcan, Svane, Inge Marie, Niemann, Carsten Utoft, Pedersen, Lars Møller, and Andersen, Mads Hald
- Subjects
CHRONIC lymphocytic leukemia ,IMMUNOGLOBULIN heavy chains ,CHRONIC leukemia ,VACCINE immunogenicity ,LYMPHOCYTE count ,VACCINE effectiveness - Abstract
Chronic lymphocytic leukemia (CLL) patients with unmutated immunoglobulin heavy chain (IgHV) are at risk of early disease progression compared to patients with mutated IgHV. As a preventive strategy, we treated 19 previously untreated CLL patients with unmutated IgHV in a phase 1/2 trial (clinicaltrials.gov, NCT03939234) exploring the efficacy and toxicity of a therapeutic cancer vaccine containing peptides derived from programmed death ligand 1 (PD-L1) and ligand 2 (PD-L2), hoping to restore immunological control of the disease. According to the International Workshop on Chronic lymphocytic Leukemia (iwCLL) response criteria, no patients obtained a response; however, during follow-up, one patient had complete normalization of the peripheral lymphocyte count and remained in biochemical remission after a follow-up time of 15 months. At the end of treatment, one patient had progressed, and 17 patients had stable disease. During follow-up with a median time of 23.5 months since inclusion, seven patients had progressed, and eight patients had stable disease. The median time to first treatment (TTFT) from diagnosis was 90.3 months with a median follow-up time of 50.1 months. This apparent favorable outcome in TTFT needs to be investigated in a randomized setting, as our population may have been biased. More than 80% of patients obtained vaccine-specific immune responses, confirming the immunogenicity of the vaccine. The vaccine was generally well tolerated with only grade I–II adverse events. Although there were some signs of clinical effects, the vaccine seems to be insufficient as monotherapy in CLL, possibly due to a high tumor burden. The efficacy of the vaccine should preferably be tested in combination with novel targeted therapies or as a consolidating treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
8. An immunogenic first-in-human immune modulatory vaccine with PD-L1 and PD-L2 peptides is feasible and shows early signs of efficacy in follicular lymphoma.
- Author
-
Klausen, Uffe, Jørgensen, Nicolai Grønne Dahlager, Grauslund, Jacob Handlos, Ahmad, Shamaila Munir, Gang, Anne Ortved, Martinenaite, Evelina, Weis-Banke, Stine Emilie, Breinholt, Marie Fredslund, Novotny, Guy Wayne, Kjeldsen, Julie Westerlin, Holmström, Morten Orebo, Pedersen, Lone Bredo, Poulsen, Christian Bjørn, Hansen, Per Boye, Met, Özcan, Svane, Inge Marie, Niemann, Carsten Utoft, Pedersen, Lars Møller, and Andersen, Mads Hald
- Subjects
FOLLICULAR lymphoma ,MONONUCLEAR leukocytes ,PROGRAMMED death-ligand 1 ,REGULATORY T cells ,PEPTIDES - Abstract
Cells in the tumor microenvironment of Follicular lymphoma (FL) express checkpoint molecules such as programmed death ligands 1 and 2 (PD-L1 and PD-L2) and are suppressing anti-tumor immune activity. Stimulation of peripheral blood mononuclear cells (PBMC) with PD-L1 (IO103) or PD-L2 (IO120) peptides can activate specific T cells inducing anti-regulatory functions including cytotoxicity against PD-L1/PD-L2-expressing cells. In this study, we vaccinated eight FL patients with PD-L1 and PD-L2 peptides following treatment with standard chemotherapy. Patients experienced grade 1-2 injection site reaction (5/8) and mild flu-like symptoms (6/8). One patient experienced neutropenia and thrombocytopenia during pseudo-progression. Enzyme-linked immunospot detected vaccine-specific immune responses in PBMC from all patients, predominately toward PD-L1. The circulating immune composition was stable during treatment; however, we observed a reduction regulatory T cells, however, not significant. One patient achieved a complete remission during vaccination and two patients had pseudo-progression followed by long-term disease regression. Further examination of these early signs of clinical efficacy of the dual-epitope vaccine in a larger study is warranted. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
9. Peptide Vaccination Against PD-L1 With IO103 a Novel Immune Modulatory Vaccine in Multiple Myeloma: A Phase I First-in-Human Trial.
- Author
-
Jørgensen, Nicolai Grønne, Klausen, Uffe, Grauslund, Jacob Handlos, Helleberg, Carsten, Aagaard, Thomas Granum, Do, Trung Hieu, Ahmad, Shamaila Munir, Olsen, Lars Rønn, Klausen, Tobias Wirenfeldt, Breinholt, Marie Fredslund, Hansen, Morten, Martinenaite, Evelina, Met, Özcan, Svane, Inge Marie, Knudsen, Lene Meldgaard, and Andersen, Mads Hald
- Subjects
PROGRAMMED death-ligand 1 ,MELPHALAN ,MULTIPLE myeloma ,CLINICAL trial registries ,VACCINATION ,VACCINE effectiveness - Abstract
Background: Immune checkpoint blockade with monoclonal antibodies targeting programmed death 1 (PD-1) and its ligand PD-L1 has played a major role in the rise of cancer immune therapy. We have identified naturally occurring self-reactive T cells specific to PD-L1 in both healthy donors and cancer patients. Stimulation with a PD-L1 peptide (IO103), activates these cells to exhibit inflammatory and anti-regulatory functions that include cytotoxicity against PD-L1–expressing target cells. This prompted the initiation of the present first-in-human study of vaccination with IO103, registered at clinicaltrials.org (NCT03042793). Methods: Ten patients with multiple myeloma who were up to 6 months after high dose chemotherapy with autologous stem cell support, were enrolled. Subcutaneous vaccinations with IO103 with the adjuvant Montanide ISA 51 was given up to fifteen times during 1 year. Safety was assessed by the common toxicity criteria for adverse events (CTCAE). Immunogenicity of the vaccine was evaluated using IFNγ enzyme linked immunospot and intracellular cytokine staining on blood and skin infiltrating lymphocytes from sites of delayed-type hypersensitivity. The clinical course was described. Results: All adverse reactions to the PD-L1 vaccine were below CTCAE grade 3, and most were grade 1–2 injection site reactions. The total rate of adverse events was as expected for the population. All patients exhibited peptide specific immune responses in peripheral blood mononuclear cells and in skin-infiltrating lymphocytes after a delayed-type hypersensitivity test. The clinical course was as expected for the population. Three of 10 patients had improvements of responses which coincided with the vaccinations. Conclusion: Vaccination against PD-L1 was associated with low toxicity and high immunogenicity. This study has prompted the initiation of later phase trials to assess the vaccines efficacy. Clinical Trial Registration: clinicaltrials.org , identifier NCT03042793. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
10. The immune checkpoint regulator PD-L1 is a specific target for naturally occurring CD4+ T cells.
- Author
-
Munir, Shamaila, Andersen, Gitte Holmen, Svane, Inge Marie, and Andersen, Mads Hald
- Subjects
T cells ,ANTIVIRAL agents ,CANCER patients ,PEPTIDES ,LYMPHOCYTES ,THERAPEUTICS - Abstract
Programmed cell death 1 ligand 1 (PD-L1) is an important regulator of T-cell responses and may consequently limit anticancer immunity. We have recently identified PD-L1-specific, cytotoxic CD8+ T cells. In the present study, we develop these findings and report that CD4+ helper T cells spontaneously recognize PD-L1. We examined the locality of a previously identified HLA-A"0201-restricted PD-L1-epitope for the presence of possible CD4+ T-cell epitopes. Thus, we identified naturally occurring PD-L1-specific CD4+ T cells among the peripheral blood lymphocytes of cancer patients and - to lesser extents - healthy donors, by means of ELISP OT assays. PD-L1-specific CD4+ T cells appeared to be T
H 17 cells exhibiting an effector T-cell cytokine profile. Hence, PD-L1-specific CD4+ T cells released interferon γ (IFNγ), tumor necrosis factor α (TNFα) and interleukin-17 (IL-17) in response to a long PD-L1-derived peptide. Furthermore, we demonstrate that the specific recognition of PD-L1 by CD4+ T cells is MHC Class II-restricted. Natural T-cell responses against PD-L1 are noteworthy as they may play a prominent role in the regulation of the immune system. Thus, cytokine release from PD-L1-specific CD4+ T cells may surmount the overall immunosuppressive actions of this immune checkpoint regulator. Moreover, PD-L1-specific T cells might be useful for anticancer immunotherapy, as they may counteract common mechanisms of immune escape mediated by the PD-L1/PD-1 pathway. [ABSTRACT FROM AUTHOR]- Published
- 2013
- Full Text
- View/download PDF
11. Vaccination against PD-L1 with IO103 a Novel Immune Modulatory Vaccine in Basal Cell Carcinoma: A Phase IIa Study.
- Author
-
Jørgensen, Nicolai Grønne, Kaae, Jeanette, Grauslund, Jacob Handlos, Met, Özcan, Nielsen, Signe Ledou, Pedersen, Ayako Wakatsuki, Svane, Inge Marie, Ehrnrooth, Eva, Andersen, Mads Hald, Zachariae, Claus, Skov, Lone, and Khan, Shaheen
- Subjects
FLOW cytometry ,IMMUNIZATION ,PROGRAMMED death-ligand 1 ,COMBINATION drug therapy ,CLINICAL trials ,PEPTIDE vaccines ,TREATMENT effectiveness ,DESCRIPTIVE statistics ,RESEARCH funding ,BASAL cell carcinoma ,IMMUNOTHERAPY ,PATIENT safety - Abstract
Simple Summary: Basal cell carcinoma is the most common skin cancer and new treatments for patients with widespread and numerous tumors are lacking. In a previous study treating patients with multiple myeloma with a peptide vaccine called IO103 against an immune checkpoint molecule called programmed death ligand 1, two cases of basal cell carcinoma regressed. The aim of the present study was to assess the effect of vaccination with IO103 in ten patients with basal cell carcinoma. Patients were vaccinated with Montanide as adjuvant up to nine times during six months. Regression in tumor size of at least 30% was seen in five of 18 tumors, two of which showed complete regression. Vaccinations resulted in immune responses against the vaccine in blood samples from nine of ten patients and in skin samples from five of nine patients. The findings suggest that the vaccine may be effective against some basal cell carcinomas. Antitumor activity of immune checkpoint blocking antibodies against programmed death 1 (PD-1) in basal cell carcinoma (BCC) has been described. IO103 is a peptide vaccine against the major PD-1 ligand PD-L1. A phase IIa study of vaccination with IO103 and Montanide adjuvant was conducted in patients with resectable BCC (NCT03714529). Vaccinations were given six times every 2 weeks (q2w), followed by three vaccines q4w in responders. Primary endpoints were clinical responses of target tumors, change in target tumor size and immune responses to the vaccine. Secondary endpoint was safety. One tumor per patient was designated target tumor and biopsied twice during the course of vaccination. Synchronous non-target BCCs were not biopsied during vaccinations. Ten patients were vaccinated (six patients received six vaccinations and four patients received nine vaccinations). A partial response (PR) was seen in two target tumors. Two complete responses (CR) and one PR were observed in eight non-target tumors in four patients. No tumors progressed. Related adverse events were grade 1 and reversible. Immune responses against IO103 were induced in blood samples from nine of ten and skin-infiltrating lymphocytes from five of the nine patients. The regressions seen in non-target tumors suggest that IO103 may be effective against a subtype of BCC. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
12. Spontaneous T-cell responses against the immune check point programmed-death-ligand 1 (PD-L1) in patients with chronic myeloproliferative neoplasms correlate with disease stage and clinical response.
- Author
-
Holmström, Morten Orebo, Riley, Caroline Hasselbalch, Skov, Vibe, Svane, Inge Marie, Hasselbalch, Hans Carl, and Andersen, Mads Hald
- Subjects
MYELOPROLIFERATIVE neoplasms ,T cells ,IMMUNE response - Abstract
The Chronic Myeloproliferative Neoplasms (MPN) are cancers characterized by hyperinflammation and immune deregulation. Concurrently, the expression of the immune check point programmed death ligand 1 (PD-L1) is induced by inflammation. In this study we report on the occurrence of spontaneous T cell responses against a PD-L1 derived epitope in patients with MPN. We show that 71% of patients display a significant immune response against PD-L1, and patients with advanced MPN have significantly fewer and weaker PD-L1 specific immune responses compared to patients with non-advanced MPN. The PD-L1 specific T cell responses are CD4
+ T cell responses, and by gene expression analysis we show that expression of PD-L1 is enhanced in patients with MPN. This could imply that the tumor specific immune response in MPN could be enhanced by vaccination with PD-L1 derived epitopes by boosting the anti-regulatory immune response hereby allowing tumor specific T cell to exert anti-tumor immunity. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
13. PD-L1 peptide co-stimulation increases immunogenicity of a dendritic cell-based cancer vaccine.
- Author
-
Munir Ahmad, Shamaila, Martinenaite, Evelina, Hansen, Morten, Junker, Niels, Borch, Troels Holz, Met, Özcan, Donia, Marco, Svane, Inge Marie, and Andersen, Mads Hald
- Subjects
T cells ,DENDRITIC cells ,EPITOPES ,CANCER vaccines ,IMMUNOTHERAPY - Abstract
We recently described naturally occurring PD-L1-specific T cells that recognize PD-L1-expressing immune cells as well as malignant cells. In the present study, we investigated whether the immunogenicity of a dendritic cell (DC)-based vaccine could be influenced by co-stimulation with a known PD-L1-derived epitope. We incubated a PD-L1-derived peptide epitope (19 amino acids long) or a control peptide (an irrelevant HIV epitope) with peripheral blood mononuclear cells from patients with malignant melanoma who had received a DC-based vaccine. We observed a significantly higher number of T cells that reacted to the vaccine in cultures that had been co-stimulated with the PD-L1 peptide epitope compared to cultures incubated with control peptide. Next, we characterized a novel PD-L1-derived epitope (23 amino acids long) and found that co-stimulation with both PD-L1 epitopes boosted the immune response elicited by the DC vaccine even further. Consequently, we observed a significant increase in the number of vaccine-reacting T cellsin vitro. In conclusion, activation of PD-L1-specific T cells may directly modulate immunogenicity of DC vaccines. Addition of PD-L1 epitopes may thus be an easily applicable and attractive option to augment the effectiveness of cancer vaccines and other immunotherapeutic agents. [ABSTRACT FROM PUBLISHER]
- Published
- 2016
- Full Text
- View/download PDF
14. Indoleamine 2,3-dioxygenase vaccination.
- Author
-
Andersen, Mads Hald and Svane, Inge Marie
- Subjects
- *
INDOLEAMINE 2,3-dioxygenase , *CANCER vaccines , *DENDRITIC cells , *NON-small-cell lung carcinoma , *CANCER patients - Abstract
Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme. Remarkably, we discovered IDO-specific T cells that can influence adaptive immune reactions in patients with cancer. Further, a recent phase I clinical trial demonstrated long-lasting disease stabilization without toxicity in patients with non-small-cell lung cancer (NSCLC) who were vaccinated with an IDO-derived HLA-A2-restricted epitope. [ABSTRACT FROM PUBLISHER]
- Published
- 2015
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.