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

Published inMolecular Therapy Oncolytics, vol. 17, p. 232-240
Publication date2020
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.

Keywords
  • CAR T cells
  • Cell therapy
  • Chimeric antigen receptor
  • Combination immunotherapy
  • Immunotherapy
  • Oncolytic virus
  • Solid tumor
  • Synthetic immunology
  • Tumor engineering
  • Vaccinia virus
Affiliation entities Not a UNIGE publication
Citation (ISO format)
AALIPOUR, Amin et al. Viral Delivery of CAR Targets to Solid Tumors Enables Effective Cell Therapy. In: Molecular Therapy Oncolytics, 2020, vol. 17, p. 232–240. doi: 10.1016/j.omto.2020.03.018
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Journal ISSN2372-7705
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Technical informations

Creation28/10/2020 09:14:00
First validation28/10/2020 09:14:00
Update15/03/2023 22:55:33
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