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Review
. 2020 Oct;26(10):1759-1769.
doi: 10.1016/j.bbmt.2020.06.020. Epub 2020 Jul 2.

Chimeric Antigen Receptor Therapy: How Are We Driving in Solid Tumors?

Uri Greenbaum  1 , Fevzi F Yalniz  1 , Samer A Srour  1 , Katayoun Rezvani  1 , Harjeet Singh  2 , Amanda Olson  1 , George Blumenschein Jr  3 , David S Hong  4 , Elizabeth J Shpall  1 , Partow Kebriaei  5
Affiliations
Review

Chimeric Antigen Receptor Therapy: How Are We Driving in Solid Tumors?

Uri Greenbaum et al. Biol Blood Marrow Transplant. 2020 Oct.

Abstract

Immune effector cell (IEC) therapy is emerging as a promising approach in the field of cancer immunotherapy. Clinical IEC trials, predominantly using chimeric antigen receptor (CAR) T cells, have shown excellent responses in CD19+ B cell malignancies and multiple myeloma. In solid tumors, preclinical data are encouraging, but clinical data are in their infancy, and there are challenges in using CAR T therapy in this setting, including (1) on-target off-tumor toxicity, (2) optimal target identification, (3) effective trafficking into bulky tumor tissue, and (4) resistance to tumor immune evasion mechanisms. Novel techniques and modifications are being explored in both the preclinical and clinical settings, aiming to improve treatment efficacy and address the aforementioned obstacles to successful CAR T therapy in solid tumors. Here we review these challenges in a clinically oriented approach and summarize published clinical trials using CAR T therapy in a variety of solid tumors.

Keywords: Cancer immunotherapy; Chimeric antigen receptor T cells; Immune effector cell therapy; Solid tumor; T cell receptor.

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Conflict of interest statement

E.J.S. serves on the scientific advisory boards of Magenta, Novartis, Celgene, Adaptimmune, and Zelluna. K.R. has a licensing agreement with Takeda; has received educational grants from Affymed and Pharmacyclics; and serves on scientific advisory boards of Virogen, Adicet Bio, Formula Pharma, and GemoAb. G.B. reports grants from Adaptimmune, Elelixis, GlaxoSmithKline, Immatics, Immunocore, Incyte, Kite Pharma, Macrogenics, and Torque; personal fees from Clovis Oncology, Abbvie, Adicet, Amgen, Ariad, Virogin Biotech, Johnson & Johnson/Janssen, and Maverick Therapeutics; and grants and personal fees from Novartis, Bayer, AstraZeneca, Bristol-Myers Squibb, Celgene, Genetech, MedImmune, Merck, Roche, and Xcovery. D.S.H. reports research/grant funding from AbbVie, Adaptimmune, Aldi-Norte, Amgen, Astra-Zeneca, Bayer, BMS, Daiichi-Sankyo, Eisai, Fate Therapeutics, Genentech, Genmab, GSK, Ignyta, Infinity, Kite, Kyowa, Lilly, LOXO, Merck, MedImmune, Mirati, miRNA, Molecular Templates, Mologen, NCI-CTEP, Novartis, Pfizer, Seattle Genetics, Takeda, Turning Point Therapeutics; has received reimbursement for travel, accommodations, and expenses from Bayer, Genmab, AACR, ASCO, SITC. Consulting or Advisory Role: Alpha Insights, Amgen, Axiom, Adaptimmune, Baxter, Bayer, eCancer, Genentech, GLG, Group H, Guidepoint, Infinity, Medscape, Numab, Oncology Education Project Association, Pfizer, Prime Oncology, Takeda, Trieza Therapeutics, and WebMD; and has other ownership interests in Molecular Match (advisor), OncoResponse (founder), and Presagia (advisor). P.K. has received research support from Amgen and Ziopharm; has served on advisory boards for Pfizer, Kite, and Novartis; and has received consulting fees from Jazz Pharmaceuticals.

Figures

Figure 1.
Figure 1.
Adoptive cell therapy. (A) CAR. (B) Fourth-generation CAR coding for cytokine production. (C) Genetically modified T cell receptor targeting tumor MHC molecules presenting tumor-derived peptides. (Some elements of this figure are adapted from servier medical art under a CC 3.0 license.)
Figure 2.
Figure 2.
Challenges with cellular therapy in solid tumors and areas of investigation and improvements in future therapies and constructs. (Some elements of this figure are adapted from servier medical art under a CC 3.0 license.)
See this image and copyright information in PMC

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