Humanized CAR T cells targeting p95HER2

Roman, M.; Rius Ruiz, I.; Grinyo-Escuer, A.; Duro-Sanchez, S.; Escorihuela, M.; Moessner, E.; Klein, C.; Arribas, J.

doi:10.1101/2022.05.20.492812

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bioRxiv · 10.1101/2022.05.20.492812

Humanized CAR T cells targeting p95HER2

Roman, M.·Rius Ruiz, I.·Grinyo-Escuer, A.·Duro-Sanchez, S.·Escorihuela, M.·Moessner, E.·Klein, C.·Arribas, J.

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Abstract

Redirection of T lymphocytes against tumor-associated or tumor-specific antigens, via bispecifc T cells engagers (BiTEs) or chimeric antigen receptors (CARs), is a successful therapeutic strategy against certain hematologic malignancies. In contrast, so far it has failed against solid tumors. Given the scarcity of tumor-specific antigens, the vast majority of BiTEs and CAR Ts developed to date have been directed against tumor-associated antigens. These are expressed in some normal tissues and, as a consequence, frequent and serious side effects caused by on-target off-tumor activity have limited the use of BiTEs and CARs in the clinic. P95HER2 is a fragment of the tyrosine kinase receptor HER2 expressed in more than 30% of HER2-amplified tumors. It has been previoulsy shown that p95HER2 is a tumor-specific antigen. Here we present the generation of CARs targeting p95HER2. p95HER2 CAR T cells show remarkable activity against p95HER2-expressing cells in vitro and in vivo. Further, they are also effective against lung and brain metastasis. These tumor-specific CAR T cells could be used in the near future to deliver additional anti-tumor therapies in a safe manner.

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Roman, M., Rius Ruiz, I., Grinyo-Escuer, A., Duro-Sanchez, S., Escorihuela, M., Moessner, E., Klein, C., Arribas, J.. 2022-05-20. Humanized CAR T cells targeting p95HER2. https://doi.org/10.1101/2022.05.20.492812

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