Search

Your search keyword '"Smits, Evelien"' showing total 732 results
Start Over Author "Smits, Evelien"
732 results on '"Smits, Evelien"'

3. Auranofin repurposing for lung and pancreatic cancer: low CA12 expression as a marker of sensitivity in patient-derived organoids, with potentiated efficacy by AKT inhibition

Author

Deben, Christophe, Boullosa, Laurie Freire, Fortes, Felicia Rodrigues, De La Hoz, Edgar Cardenas, Le Compte, Maxim, Seghers, Sofie, Peeters, Marc, Vanlanduit, Steve, Lin, Abraham, Dijkstra, Krijn K., Van Schil, Paul, Hendriks, Jeroen M. H., Prenen, Hans, Roeyen, Geert, Lardon, Filip, and Smits, Evelien

Published
2024
Full Text
View/download PDF

4. IL-15-secreting CAR natural killer cells directed toward the pan-cancer target CD70 eliminate both cancer cells and cancer-associated fibroblasts

Author

Van den Eynde, Astrid, Gehrcken, Laura, Verhezen, Tias, Lau, Ho Wa, Hermans, Christophe, Lambrechts, Hilde, Flieswasser, Tal, Quatannens, Delphine, Roex, Gils, Zwaenepoel, Karen, Marcq, Elly, Joye, Philippe, Cardenas De La Hoz, Edgar, Deben, Christophe, Gasparini, Alessia, Montay-Gruel, Pierre, Le Compte, Maxim, Lion, Eva, Lardon, Filip, Van Laere, Steven, Siozopoulou, Vasiliki, Campillo-Davo, Diana, De Waele, Jorrit, Pauwels, Patrick, Jacobs, Julie, Smits, Evelien, and Van Audenaerde, Jonas R. M.

Published
2024
Full Text
View/download PDF

7. Lack of functional TCR-epitope interaction is associated with herpes zoster through reduced downstream T cell activation

Author

Boeren, Marlies, de Vrij, Nicky, Ha, My K., Valkiers, Sebastiaan, Souquette, Aisha, Gielis, Sofie, Kuznetsova, Maria, Schippers, Jolien, Bartholomeus, Esther, Van den Bergh, Johan, Michels, Nele, Aerts, Olivier, Leysen, Julie, Bervoets, An, Lambert, Julien, Leuridan, Elke, Wens, Johan, Peeters, Karin, Emonds, Marie-Paule, Elias, George, Vandamme, Niels, Jansens, Hilde, Adriaensen, Wim, Suls, Arvid, Vanhee, Stijn, Hens, Niel, Smits, Evelien, Van Damme, Pierre, Thomas, Paul G., Beutels, Philippe, Ponsaerts, Peter, Van Tendeloo, Viggo, Delputte, Peter, Laukens, Kris, Meysman, Pieter, and Ogunjimi, Benson

Published
2024
Full Text
View/download PDF

11. Training of epitope-TCR prediction models with healthy donor-derived cancer-specific T cells

Author

Flumens, Donovan, primary, Gielis, Sofie, additional, Bartholomeus, Esther, additional, Campillo-Davo, Diana, additional, van der Heijden, Sanne, additional, Versteven, Maarten, additional, De Reu, Hans, additional, Smits, Evelien, additional, Ogunjimi, Benson, additional, Laukens, Kris, additional, Meysman, Pieter, additional, and Lion, Eva, additional

Published
2023
Full Text
View/download PDF

16. Capturing the heterogeneity of the pancreatic ductal adenocarcinoma tumor microenvironment: novel triple co-culture spheroids for drug screening and angiogenic evaluation

Author

Verloy, Ruben, primary, Privat-Maldonado, Angela, additional, Audenaerde, Jonas Van, additional, Rovers, Sophie, additional, Zaryouh, Hannah, additional, De Waele, Jorrit, additional, Deben, Christophe, additional, Smits, Evelien, additional, and Bogaerts, Annemie, additional

Published
2024
Full Text
View/download PDF

21. Injectable Plasma‐Treated Alginate Hydrogel for Oxidative Stress Delivery to Induce Immunogenic Cell Death in Osteosarcoma.

Author

Živanić, Milica, Espona‐Noguera, Albert, Verswyvel, Hanne, Smits, Evelien, Bogaerts, Annemie, Lin, Abraham, and Canal, Cristina

Subjects
COLD atmospheric plasmas, CELL death, ALGINIC acid, OXIDATIVE stress, LOW temperature plasmas
Abstract

Cold atmospheric plasma (CAP) is a source of cell‐damaging oxidant molecules that may be used as low‐cost cancer treatment with minimal side effects. Liquids treated with cold plasma and enriched with oxidants are a modality for non‐invasive treatment of internal tumors with cold plasma via injection. However, liquids are easily diluted with body fluids which impedes high and localized delivery of oxidants to the target. As an alternative, plasma‐treated hydrogels (PTH) emerge as vehicles for the precise delivery of oxidants. This study reports an optimal protocol for the preparation of injectable alginate PTH that ensures the preservation of plasma‐generated oxidants. The generation, storage, and release of oxidants from the PTH are assessed. The efficacy of the alginate PTH in cancer treatment is demonstrated in the context of cancer cell cytotoxicity and immunogenicity–release of danger signals and phagocytosis by immature dendritic cells, up to now unexplored for PTH. These are shown in osteosarcoma, a hard‐to‐treat cancer. The study aims to consolidate PTH as a novel cold plasma treatment modality for non‐invasive or postoperative tumor treatment. The results offer a rationale for further exploration of alginate‐based PTHs as a versatile platform in biomedical engineering. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

23. Analysis of Wilms' tumor protein 1 specific TCR repertoire in AML patients uncovers higher diversity in patients in remission than in relapsed

Author

Gielis, Sofie, primary, Flumens, Donovan, additional, van der Heijden, Sanne, additional, Versteven, Maarten, additional, De Reu, Hans, additional, Bartholomeus, Esther, additional, Schippers, Jolien, additional, Campillo-Davo, Diana, additional, Berneman, Zwi, additional, Anguille, Sébastien, additional, Smits, Evelien, additional, Ogunjimi, Benson, additional, Lion, Eva, additional, Laukens, Kris, additional, and Meysman, Pieter, additional

Published
2023
Full Text
View/download PDF

26. Trial watch: chemotherapy-induced immunogenic cell death in oncology

Author

Sprooten, Jenny, Laureano, Raquel S., Vanmeerbeek, Isaure, Govaerts, Jannes, Naulaerts, Stefan, Borras, Daniel M., Kinget, Lisa, Fucikova, Jitka, Spisek, Radek, Jelinkova, Lenka Palova, Kepp, Oliver, Kroemer, Guido, Krysko, Dmitri V., Coosemans, An, Vaes, Rianne D.W., De Ruysscher, Dirk, De Vleeschouwer, Steven, Wauters, Els, Smits, Evelien, Tejpar, Sabine, Beuselinck, Benoit, Hatse, Sigrid, Wildiers, Hans, Clement, Paul M., Vandenabeele, Peter, Zitvogel, Laurence, and Garg, Abhishek D.

Subjects
dendritic cell, Immunology, chemotherapy, danger signals, ENDOPLASMIC-RETICULUM STRESS, immunogenic cell death, Medicine and Health Sciences, ANTITUMOR IMMUNITY, cancer, antigen-presenting cells, immune-checkpoint blockers, DAMPs, CAR T cells, CALRETICULIN EXPOSURE, Science & Technology, I INTERFERON, HIGH-MOBILITY GROUP, Biology and Life Sciences, ER STRESS, SOLID TUMORS, NEGATIVE BREAST-CANCER, Oncology, cancer therapy, Human medicine, trial watch, immunotherapy, Life Sciences & Biomedicine, MESOTHELIN
Abstract

Immunogenic cell death (ICD) refers to an immunologically distinct process of regulated cell death that activates, rather than suppresses, innate and adaptive immune responses. Such responses culminate into T cell-driven immunity against antigens derived from dying cancer cells. The potency of ICD is dependent on the immunogenicity of dying cells as defined by the antigenicity of these cells and their ability to expose immunostimulatory molecules like damage-associated molecular patterns (DAMPs) and cytokines like type I interferons (IFNs). Moreover, it is crucial that the host's immune system can adequately detect the antigenicity and adjuvanticity of these dying cells. Over the years, several well-known chemotherapies have been validated as potent ICD inducers, including (but not limited to) anthracyclines, paclitaxels, and oxaliplatin. Such ICD-inducing chemotherapeutic drugs can serve as important combinatorial partners for anti-cancer immunotherapies against highly immuno-resistant tumors. In this Trial Watch, we describe current trends in the preclinical and clinical integration of ICD-inducing chemotherapy in the existing immuno-oncological paradigms. ispartof: ONCOIMMUNOLOGY vol:12 issue:1 ispartof: location:United States status: accepted

Published
2023

30. Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia

Author

Anguille, Sébastien, Van de Velde, Ann L., Smits, Evelien L., Van Tendeloo, Viggo F., Juliusson, Gunnar, Cools, Nathalie, Nijs, Griet, Stein, Barbara, Lion, Eva, Van Driessche, Ann, Vandenbosch, Irma, Verlinden, Anke, Gadisseur, Alain P., Schroyens, Wilfried A., Muylle, Ludo, Vermeulen, Katrien, Maes, Marie-Berthe, Deiteren, Kathleen, Malfait, Ronald, Gostick, Emma, Lammens, Martin, Couttenye, Marie M., Jorens, Philippe, Goossens, Herman, Price, David A., Ladell, Kristin, Oka, Yoshihiro, Fujiki, Fumihiro, Oji, Yusuke, Sugiyama, Haruo, and Berneman, Zwi N.

Published
2017
Full Text
View/download PDF

31. Increased herpes zoster risk associated with poor HLA-A immediate early 62 protein (IE62) affinity

Author

Meysman, Pieter, De Neuter, Nicolas, Bartholomeus, Esther, Elias, George, Van den Bergh, Johan, Emonds, Marie-Paule, Haasnoot, Geert W., Heynderickx, Steven, Wens, Johan, Michels, Nele R., Lambert, Julien, Lion, Eva, Claas, Frans H. J., Goossens, Herman, Smits, Evelien, Van Damme, Pierre, Van Tendeloo, Viggo, Beutels, Philippe, Suls, Arvid, Mortier, Geert, Laukens, Kris, and Ogunjimi, Benson

Published
2018
Full Text
View/download PDF

33. Data from Humoral and Cellular Immune Responses against SARS-CoV-2 after Third Dose BNT162b2 following Double-Dose Vaccination with BNT162b2 versus ChAdOx1 in Patients with Cancer

Author

Debie, Yana, primary, Van Audenaerde, Jonas R.M., primary, Vandamme, Timon, primary, Croes, Lieselot, primary, Teuwen, Laure-Anne, primary, Verbruggen, Lise, primary, Vanhoutte, Greetje, primary, Marcq, Elly, primary, Verheggen, Lisa, primary, Le Blon, Debbie, primary, Peeters, Bart, primary, Goossens, Maria E., primary, Pannus, Pieter, primary, Ariën, Kevin K., primary, Anguille, Sébastien, primary, Janssens, Annelies, primary, Prenen, Hans, primary, Smits, Evelien L.J., primary, Vulsteke, Christof, primary, Lion, Eva, primary, Peeters, Marc, primary, and van Dam, Peter A., primary

Published
2023
Full Text
View/download PDF

34. Figure S1 from Humoral and Cellular Immune Responses against SARS-CoV-2 after Third Dose BNT162b2 following Double-Dose Vaccination with BNT162b2 versus ChAdOx1 in Patients with Cancer

Author

Debie, Yana, primary, Van Audenaerde, Jonas R.M., primary, Vandamme, Timon, primary, Croes, Lieselot, primary, Teuwen, Laure-Anne, primary, Verbruggen, Lise, primary, Vanhoutte, Greetje, primary, Marcq, Elly, primary, Verheggen, Lisa, primary, Le Blon, Debbie, primary, Peeters, Bart, primary, Goossens, Maria E., primary, Pannus, Pieter, primary, Ariën, Kevin K., primary, Anguille, Sébastien, primary, Janssens, Annelies, primary, Prenen, Hans, primary, Smits, Evelien L.J., primary, Vulsteke, Christof, primary, Lion, Eva, primary, Peeters, Marc, primary, and van Dam, Peter A., primary

Published
2023
Full Text
View/download PDF

35. Supplementary Tables S1-S2 from Humoral and Cellular Immune Responses against SARS-CoV-2 after Third Dose BNT162b2 following Double-Dose Vaccination with BNT162b2 versus ChAdOx1 in Patients with Cancer

Author

Debie, Yana, primary, Van Audenaerde, Jonas R.M., primary, Vandamme, Timon, primary, Croes, Lieselot, primary, Teuwen, Laure-Anne, primary, Verbruggen, Lise, primary, Vanhoutte, Greetje, primary, Marcq, Elly, primary, Verheggen, Lisa, primary, Le Blon, Debbie, primary, Peeters, Bart, primary, Goossens, Maria E., primary, Pannus, Pieter, primary, Ariën, Kevin K., primary, Anguille, Sébastien, primary, Janssens, Annelies, primary, Prenen, Hans, primary, Smits, Evelien L.J., primary, Vulsteke, Christof, primary, Lion, Eva, primary, Peeters, Marc, primary, and van Dam, Peter A., primary

Published
2023
Full Text
View/download PDF

36. Injectable plasma-treated alginate hydrogel for oxidative stress delivery to induce immunogenic cell death in osteosarcoma

Author

Universitat Politècnica de Catalunya. Doctorat en Enginyeria Biomèdica, Universitat Politècnica de Catalunya. Departament de Ciència i Enginyeria de Materials, Universitat Politècnica de Catalunya. BBT - Grup de recerca en Biomaterials, Biomecànica i Enginyeria de Teixits, Zivanic, Milica, Espona Noguera, Albert, Verswyvel, Hanne, Smits, Evelien, Bogaerts, Annemie, Canal Barnils, Cristina, Lin, Abraham, Universitat Politècnica de Catalunya. Doctorat en Enginyeria Biomèdica, Universitat Politècnica de Catalunya. Departament de Ciència i Enginyeria de Materials, Universitat Politècnica de Catalunya. BBT - Grup de recerca en Biomaterials, Biomecànica i Enginyeria de Teixits, Zivanic, Milica, Espona Noguera, Albert, Verswyvel, Hanne, Smits, Evelien, Bogaerts, Annemie, Canal Barnils, Cristina, and Lin, Abraham

Abstract

Cold atmospheric plasma (CAP) is a source of cell-damaging oxidant molecules that may be used as low-cost cancer treatment with minimal side effects. Liquids treated with cold plasma and enriched with oxidants are a modality for non-invasive treatment of internal tumors with cold plasma via injection. However, liquids are easily diluted with body fluids which impedes high and localized delivery of oxidants to the target. As an alternative, plasma-treated hydrogels (PTH) emerge as vehicles for the precise delivery of oxidants. This study reports an optimal protocol for the preparation of injectable alginate PTH that ensures the preservation of plasma-generated oxidants. The generation, storage, and release of oxidants from the PTH are assessed. The efficacy of the alginate PTH in cancer treatment is demonstrated in the context of cancer cell cytotoxicity and immunogenicity–release of danger signals and phagocytosis by immature dendritic cells, up to now unexplored for PTH. These are shown in osteosarcoma, a hard-to-treat cancer. The study aims to consolidate PTH as a novel cold plasma treatment modality for non-invasive or postoperative tumor treatment. The results offer a rationale for further exploration of alginate-based PTHs as a versatile platform in biomedical engineering., Peer Reviewed, Objectius de Desenvolupament Sostenible::3 - Salut i Benestar, Postprint (published version)

Published
2023

37. Trial watch:chemotherapy-induced immunogenic cell death in oncology

Author

Sprooten, Jenny, Laureano, Raquel S., Vanmeerbeek, Isaure, Govaerts, Jannes, Naulaerts, Stefan, Borras, Daniel M., Kinget, Lisa, Fucíková, Jitka, Špíšek, Radek, Jelínková, Lenka Palová, Kepp, Oliver, Kroemer, Guido, Krysko, Dmitri V., Coosemans, An, Vaes, Rianne D.W., De Ruysscher, Dirk, De Vleeschouwer, Steven, Wauters, Els, Smits, Evelien, Tejpar, Sabine, Beuselinck, Benoit, Hatse, Sigrid, Wildiers, Hans, Clement, Paul M., Vandenabeele, Peter, Zitvogel, Laurence, Garg, Abhishek D., Sprooten, Jenny, Laureano, Raquel S., Vanmeerbeek, Isaure, Govaerts, Jannes, Naulaerts, Stefan, Borras, Daniel M., Kinget, Lisa, Fucíková, Jitka, Špíšek, Radek, Jelínková, Lenka Palová, Kepp, Oliver, Kroemer, Guido, Krysko, Dmitri V., Coosemans, An, Vaes, Rianne D.W., De Ruysscher, Dirk, De Vleeschouwer, Steven, Wauters, Els, Smits, Evelien, Tejpar, Sabine, Beuselinck, Benoit, Hatse, Sigrid, Wildiers, Hans, Clement, Paul M., Vandenabeele, Peter, Zitvogel, Laurence, and Garg, Abhishek D.

Abstract

Immunogenic cell death (ICD) refers to an immunologically distinct process of regulated cell death that activates, rather than suppresses, innate and adaptive immune responses. Such responses culminate into T cell-driven immunity against antigens derived from dying cancer cells. The potency of ICD is dependent on the immunogenicity of dying cells as defined by the antigenicity of these cells and their ability to expose immunostimulatory molecules like damage-associated molecular patterns (DAMPs) and cytokines like type I interferons (IFNs). Moreover, it is crucial that the host’s immune system can adequately detect the antigenicity and adjuvanticity of these dying cells. Over the years, several well-known chemotherapies have been validated as potent ICD inducers, including (but not limited to) anthracyclines, paclitaxels, and oxaliplatin. Such ICD-inducing chemotherapeutic drugs can serve as important combinatorial partners for anti-cancer immunotherapies against highly immuno-resistant tumors. In this Trial Watch, we describe current trends in the preclinical and clinical integration of ICD-inducing chemotherapy in the existing immuno-oncological paradigms.

Published
2023

38. Supplementary Figures S1-S12 from Expansion of a BDCA1+CD14+ Myeloid Cell Population in Melanoma Patients May Attenuate the Efficacy of Dendritic Cell Vaccines

Author

Bakdash, Ghaith, primary, Buschow, Sonja I., primary, Gorris, Mark A.J., primary, Halilovic, Altuna, primary, Hato, Stanleyson V., primary, Sköld, Annette E., primary, Schreibelt, Gerty, primary, Sittig, Simone P., primary, Torensma, Ruurd, primary, Duiveman-de Boer, Tjitske, primary, Schröder, Christoph, primary, Smits, Evelien L., primary, Figdor, Carl G., primary, and de Vries, I. Jolanda M., primary

Published
2023
Full Text
View/download PDF

39. Supplementary Dataset S1 from Expansion of a BDCA1+CD14+ Myeloid Cell Population in Melanoma Patients May Attenuate the Efficacy of Dendritic Cell Vaccines

Author

Bakdash, Ghaith, primary, Buschow, Sonja I., primary, Gorris, Mark A.J., primary, Halilovic, Altuna, primary, Hato, Stanleyson V., primary, Sköld, Annette E., primary, Schreibelt, Gerty, primary, Sittig, Simone P., primary, Torensma, Ruurd, primary, Duiveman-de Boer, Tjitske, primary, Schröder, Christoph, primary, Smits, Evelien L., primary, Figdor, Carl G., primary, and de Vries, I. Jolanda M., primary

Published
2023
Full Text
View/download PDF

40. Supplementary Table and Figure Legends from Expansion of a BDCA1+CD14+ Myeloid Cell Population in Melanoma Patients May Attenuate the Efficacy of Dendritic Cell Vaccines

Author

Bakdash, Ghaith, primary, Buschow, Sonja I., primary, Gorris, Mark A.J., primary, Halilovic, Altuna, primary, Hato, Stanleyson V., primary, Sköld, Annette E., primary, Schreibelt, Gerty, primary, Sittig, Simone P., primary, Torensma, Ruurd, primary, Duiveman-de Boer, Tjitske, primary, Schröder, Christoph, primary, Smits, Evelien L., primary, Figdor, Carl G., primary, and de Vries, I. Jolanda M., primary

Published
2023
Full Text
View/download PDF

41. Supplementary Table S2 from Expansion of a BDCA1+CD14+ Myeloid Cell Population in Melanoma Patients May Attenuate the Efficacy of Dendritic Cell Vaccines

Author

Bakdash, Ghaith, primary, Buschow, Sonja I., primary, Gorris, Mark A.J., primary, Halilovic, Altuna, primary, Hato, Stanleyson V., primary, Sköld, Annette E., primary, Schreibelt, Gerty, primary, Sittig, Simone P., primary, Torensma, Ruurd, primary, Duiveman-de Boer, Tjitske, primary, Schröder, Christoph, primary, Smits, Evelien L., primary, Figdor, Carl G., primary, and de Vries, I. Jolanda M., primary

Published
2023
Full Text
View/download PDF

42. Inactivation of SARS-CoV-2 and Other Enveloped and Non-Enveloped Viruses with Non-Thermal Plasma for Hospital Disinfection

Author

Sahun, Maxime, primary, Privat-Maldonado, Angela, additional, Lin, Abraham, additional, De Roeck, Naomi, additional, Van der Heyden, Lisa, additional, Hillen, Michaël, additional, Michiels, Johan, additional, Steenackers, Gunther, additional, Smits, Evelien, additional, Ariën, Kevin K., additional, Jorens, Philippe G., additional, Delputte, Peter, additional, and Bogaerts, Annemie, additional

Published
2023
Full Text
View/download PDF

43. Targeting CD70 in combination with chemotherapy to enhance the anti-tumor immune effects in non-small cell lung cancer

Author

Flieswasser, Tal, primary, Van den Eynde, Astrid, additional, Freire Boullosa, Laurie, additional, Melis, Jöran, additional, Hermans, Christophe, additional, Merlin, Céline, additional, Lau, Ho Wa, additional, Van Audenaerde, Jonas, additional, Lardon, Filip, additional, Smits, Evelien, additional, Pauwels, Patrick, additional, and Jacobs, Julie, additional

Published
2023
Full Text
View/download PDF

44. Auranofin Synergizes with the PARP Inhibitor Olaparib to Induce ROS-Mediated Cell Death in Mutant p53 Cancers

Author

Freire Boullosa, Laurie, primary, Van Loenhout, Jinthe, additional, Flieswasser, Tal, additional, Hermans, Christophe, additional, Merlin, Céline, additional, Lau, Ho Wa, additional, Marcq, Elly, additional, Verschuuren, Marlies, additional, De Vos, Winnok H., additional, Lardon, Filip, additional, Smits, Evelien L. J., additional, and Deben, Christophe, additional

Published
2023
Full Text
View/download PDF

45. In vitro expansion of Wilms’ tumor protein 1 epitope-specific primary T cells from healthy human peripheral blood mononuclear cells

Author

van der Heijden, Sanne, primary, Flumens, Donovan, additional, Versteven, Maarten, additional, Peeters, Stefanie, additional, Reu, Hans De, additional, Campillo-Davo, Diana, additional, Willemen, Yannick, additional, Ogunjimi, Benson, additional, Van Tendeloo, Viggo, additional, Berneman, Zwi N., additional, Anguille, Sébastien, additional, Smits, Evelien, additional, and Lion, Eva, additional

Published
2023
Full Text
View/download PDF

46. Uncovering the hidden threat: single-organoid analysis reveals clinically relevant treatment-resistant and invasive subclones in pancreatic cancer

Author

Compte, Maxim Le, primary, Cardenas De La Hoz, Edgar, additional, Peeters, Sofía, additional, Rodrigues Fortes, Felicia, additional, Hermans, Christophe, additional, Domen, Andreas, additional, Smits, Evelien, additional, Lardon, Filip, additional, Vandamme, Timon, additional, Lin, Abraham, additional, Vanlanduit, Steve, additional, Roeyen, Geert, additional, Van Laere, Steven, additional, Prenen, Hans, additional, Peeters, Marc, additional, and Deben, Christophe, additional

Published
2023
Full Text
View/download PDF

47. Challenges in neoantigen-directed therapeutics

Author

Lybaert, Lien, primary, Lefever, Steve, additional, Fant, Bruno, additional, Smits, Evelien, additional, De Geest, Bruno, additional, Breckpot, Karine, additional, Dirix, Luc, additional, Feldman, Steven A., additional, van Criekinge, Wim, additional, Thielemans, Kris, additional, van der Burg, Sjoerd H., additional, Ott, Patrick A., additional, and Bogaert, Cedric, additional

Published
2023
Full Text
View/download PDF

50. Site-specific ⁶⁸Ga-labeled nanobody for PET imaging of CD70 expression in preclinical tumor models

Author

Dewulf, Jonatan, Flieswasser, Tal, Delahaye, Tim, Vangestel, Christel, Miranda Menchaca, Alan, de Haard, Hans, Jacobs, Julie, Smits, Evelien, van den Wyngaert, Tim, and Elvas, Filipe

Subjects
Computer. Automation, Chemistry, Pharmacology. Therapy
Abstract

BackgroundCD70-CD27 is a costimulatory ligand-receptor pair in the tumor necrosis factor receptor family. With only limited expression in normal tissues, CD70 is constitutively expressed in a variety of solid tumors and hematologic malignancies, facilitating immunosuppression through CD27 signaling in the tumor microenvironment by enhanced survival of regulatory T cells, induction of T cell apoptosis, and T cell exhaustion. Consequently, CD70 is an increasingly recognized target for developing antibody-based therapies, but its expression patterns vary among different tumor types in spatial distribution, magnitude of expression and percentage of positive cells. In that regard, individual confirmation of CD70 expression at screening and during treatment could enhance the successful implementation of anti-CD70 therapies. Here, we developed a gallium-68 (Ga-68) radiolabeled single-domain antibody-fragment targeting CD70 for in vivo positron emission tomography (PET) imaging.ResultsAn anti-CD70 VHH construct containing a C-direct-tag with a free thiol was developed to enable site-specific conjugation to a NOTA bifunctional chelator for Ga-68 radiolabeling. [Ga-68]Ga-NOTA-anti-CD70 VHH was obtained in good radiochemical yield of 30.4 +/- 1.7% and high radiochemical purity (> 94%). The radiolabeled VHH showed excellent in vitro and in vivo stability. Specific binding of [Ga-68]Ga-NOTA-anti-CD70 VHH was observed on CD70(high) 786-O cells, showing significantly higher cell-associated activity when compared to the blocking condition (p < 0.0001) and CD70(low) NCl-H1975 cells (p < 0.0001). PET imaging showed specific radiotracer accumulation in CD70 expressing human tumor xenografts, which was efficiently blocked by prior injection of unlabeled anti-CD70 VHH (p = 0.0029). In addition, radiotracer uptake in CD70(high) tumors was significantly higher when compared with CD70(low) tumors (p < 0.0001). The distribution of the radioactivity in the tumors using autoradiography was spatially matched with immunohistochemistry analysis of CD70 expression.Conclusion[Ga-68]Ga-NOTA-anti-CD70 VHH showed excellent in vivo targeting of CD70 in human cancer xenografts. PET imaging using this radioimmunoconjugate holds promise as a non-invasive method to identify and longitudinally follow-up patients who will benefit most from anti-CD70 therapies.

Published
2023

Catalog

Books, media, physical & digital resources
See catalog results