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


ABSTRACT: 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.

SUBMITTER: Aalipour A 

PROVIDER: S-EPMC7183102 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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

Aalipour Amin A   Le Boeuf Fabrice F   Tang Matthew M   Murty Surya S   Simonetta Federico F   Lozano Alexander X AX   Shaffer Travis M TM   Bell John C JC   Gambhir Sanjiv S SS  

Molecular therapy oncolytics 20200407


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 ce  ...[more]

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