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

Amin Aalipour; Fabrice Le Boeuf; Matthew Tang; Surya Murty; Federico Simonetta; Alexander X. Lozano; Travis M. Shaffer; John C. Bell; Sanjiv S. Gambhir

Molecular Therapy: Oncolytics (Jun 2020)

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

Amin Aalipour,
Fabrice Le Boeuf,
Matthew Tang,
Surya Murty,
Federico Simonetta,
Alexander X. Lozano,
Travis M. Shaffer,
John C. Bell,
Sanjiv S. Gambhir

Affiliations

Amin Aalipour: Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA; Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA 94305, USA
Fabrice Le Boeuf: Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Matthew Tang: Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Surya Murty: Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA; Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA 94305, USA
Federico Simonetta: Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
Alexander X. Lozano: Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305, USA; Faculty of Medicine, University of Toronto, Toronto, ON MS5 1A8, Canada
Travis M. Shaffer: Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA
John C. Bell: Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Sanjiv S. Gambhir: Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA; Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305, USA; Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, CA 94305, USA; Corresponding author: Sanjiv S. Gambhir, Department of Bioengineering, Stanford University School of Medicine, The James H. Clark Center, 318 Campus Drive, Room E150A, Stanford, CA 94305, USA.

Journal volume & issue: Vol. 17
pp. 232 – 240

Abstract

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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.

Published in Molecular Therapy: Oncolytics

ISSN: 2372-7705 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: http://www.cell.com/molecular-therapy-family/oncolytics/latest-content

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