Abstract
Uniform and strong expression of CD19, a cell surface antigen, on cells of B-cell lineage is unique to hematologic malignancies. Tumor-associated antigen (TAA) targets in solid tumors exhibit heterogeneity with regards to intensity and distribution, posing a challenge for chimeric antigen receptor (CAR) T-cell therapy. Novel CAR designs, such as dual TAA-targeted CARs, tandem CARs, and switchable CARs, in conjunction with inhibitory CARs, are being investigated as means to overcome antigen heterogeneity. In addition to heterogeneity in cancer-cell antigen expression, the key determinants for antitumor responses are CAR expression levels and affinity in T cells. Herein, we review CAR T-cell therapy clinical trials for patients with lung or pancreatic cancers, and provide detailed translational strategies to overcome antigen heterogeneity.
Copyright © 2018 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Review
MeSH terms
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Animals
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Antigens, Neoplasm / immunology*
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Gene Expression Regulation, Neoplastic
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Humans
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Immunotherapy, Adoptive
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Lung Neoplasms / genetics
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Lung Neoplasms / immunology
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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Lymphocyte Activation
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Neoplasms / genetics
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Neoplasms / immunology*
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Neoplasms / metabolism*
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Neoplasms / therapy
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Pancreatic Neoplasms / genetics
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Pancreatic Neoplasms / immunology
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Pancreatic Neoplasms / metabolism
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Pancreatic Neoplasms / pathology
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Receptors, Antigen, T-Cell / immunology*
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Receptors, Antigen, T-Cell / metabolism*
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Receptors, Chimeric Antigen / metabolism
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism*
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Tumor Escape / immunology
Substances
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Antigens, Neoplasm
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Receptors, Antigen, T-Cell
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Receptors, Chimeric Antigen