Journal
BRITISH JOURNAL OF CANCER
Volume 120, Issue 1, Pages 79-87Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41416-018-0341-1
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Funding
- Wilhelm Sander Stiftung
- Engelhorn-Foundation
- Forderprogramm fur Forschung und Lehre
- international doctoral program i-Target: Immunotargeting of cancer - Elite Network of Bavaria
- Melanoma Research Alliance [409510]
- Marie-Sklodowska-Curie Training Network for the Immunotherapy of Cancer (IMMUTRAIN) - H2020 program of the European Union
- Else Kroner-Fresenius-Stiftung
- German Cancer Aid
- Ernst-Jung-Stiftung
- LMU Munich's Institutional Strategy LMUexcellent
- Bundesministerium fur Bildung und Forschung VIP + grant ONKATTRACT
- German Research Foundation (DFG) [DU1522-1/1]
- European Research Council [756017]
- Deutsche Jose Carreras Leukamie-Stiftung
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BACKGROUND: CD16-chimeric antigen receptors (CAR) T cells recognise the Fc-portion of therapeutic antibodies, which can enable the selective targeting of different antigens. Limited evidence exists as to which CD16-CAR design and antibody partner might be most effective. We have hypothesised that the use of high-affinity CD16 variants, with increased Fc-terminus antibody affinity, combined with Fc-engineered antibodies, would provide superior CD16-CAR T cell efficacy. METHODS: CD16-CAR T (wild-type or variants) cells were co-cultured with Panc-1 pancreatic cancer, Raji lymphoma or A375 melanoma cells in the presence or absence of anti-CD20, anti-MCSP, wild-type or the glycoengineered antibody variants. The endpoints were proliferation, activation, and cytotoxicity in vitro. RESULTS: The CD16 158 V variant of CD16-CAR T cells showed increased cytotoxic activity against all the tested cancer cells in the presence of the wild-type antibody directed against MCSP or CD20. Glycoengineered antibodies enhanced CD16-CAR T cell activity irrespective of CD16 polymorphisms as compared with the wild-type antibody. The combination of the glycoengineered antibodies with the CD16-CAR 158V variant synergised as seen by the increase in all endpoints. CONCLUSION: These results indicate that CD16-CAR with the high-affinity CD16 variant 158V, combined with Fc-engineered antibodies, have high anti-tumour efficacy.
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