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Viral Delivery of CAR Targets to Solid Tumors Enables Effective Cell Therapy

Chimeric antigen receptor (CAR) T cell therapy has had limited efficacy for solid tumors, largely due to a lack of selectively and highly expressed surface antigens. To avoid reliance on a tumor’s endogenous antigens, here we describe a method of tumor-selective delivery of surface antigens using an...

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Detalles Bibliográficos
Autores principales: Aalipour, Amin, Le Boeuf, Fabrice, Tang, Matthew, Murty, Surya, Simonetta, Federico, Lozano, Alexander X., Shaffer, Travis M., Bell, John C., Gambhir, Sanjiv S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183102/
https://www.ncbi.nlm.nih.gov/pubmed/32346612
http://dx.doi.org/10.1016/j.omto.2020.03.018
Descripción
Sumario:Chimeric antigen receptor (CAR) T cell therapy has had limited efficacy for solid tumors, largely due to a lack of selectively and highly expressed surface antigens. To avoid reliance on a tumor’s endogenous antigens, here we describe a method of tumor-selective delivery of surface antigens using an oncolytic virus to enable a generalizable CAR T cell therapy. Using CD19 as our proof of concept, we engineered a thymidine kinase-disrupted vaccinia virus to selectively deliver CD19 to malignant cells, and thus demonstrated potentiation of CD19 CAR T cell activity against two tumor types in vitro. In an immunocompetent model of B16 melanoma, this combination markedly delayed tumor growth and improved median survival compared with antigen-mismatched combinations. We also found that CD19 delivery could improve CAR T cell activity against tumor cells that express low levels of cognate antigen, suggesting a potential application in counteracting antigen-low escape. This approach highlights the potential of engineering tumors for effective adoptive cell therapy.