Engineering for Success: Approaches to Improve Chimeric Antigen Receptor T Cell Therapy for Solid Tumors

Drugs
Melinda Mata, Stephen Gottschalk

Abstract

While impressive clinical responses have been observed using chimeric antigen receptor (CAR) T cells targeting CD19+ hematologic malignancies, limited clinical benefit has been observed using CAR T cells for a variety of solid tumors. Results of clinical studies have highlighted several obstacles which CAR T cells face in the context of solid tumors, including insufficient homing to tumor sites, lack of expansion and persistence, encountering a highly immunosuppressive tumor microenvironment, and heterogeneous antigen expression. In this review, we review clinical outcomes and discuss strategies to improve the antitumor activity of CAR T cells for solid tumors.

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Citations

May 11, 2019·PloS One·Michael E BregenzerGeeta Mehta
Mar 11, 2020·Journal for Immunotherapy of Cancer·Orit ItzhakiMichal J Besser
Mar 21, 2020·Cancer Discovery·Robbie G MajznerCrystal L Mackall
Sep 25, 2020·Journal of Pharmaceutical Sciences·Lucas GutierrezMichael J Abernathy
Nov 7, 2020·Archivum Immunologiae Et Therapiae Experimentalis·Katarzyna SkorkaKrzysztof Giannopoulos

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Methods Mentioned

BETA
genetic modification
lymphodepletion
transgenic
xenograft
genetic
genetic modifications

Clinical Trials Mentioned

NCT01853631
NCT01109095
NCT01953900
NCT02652910
NCT02498912
NCT01740557
NCT02442297
NCT01818323
NCT02414269
NCT01722149

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