Immunotherapy is a promising field that harnesses the power of the immune system as
a therapeutic agent for cancer treatment. Beneficial outcomes shown in patients with
non–small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM) with relatively
higher tumor-infiltrating T cells, combined with impressive responses obtained in
a cohort of patients with NSCLC following checkpoint blockade therapy, lays a strong
foundation to promote effector immune responses in these patients. One such approach
being investigated is administration of tumor antigen-targeted T cells with transduction
of a chimeric antigen receptor (CAR). CARs are synthetic receptors that enhance T-cell
antitumor effector function and have gained momentum to investigate in solid tumors
based on recent successes of clinical trials treating patients with B-cell hematologic
malignancies. This review summarizes target antigens for CAR T-cell therapy that are
being investigated in preclinical studies and clinical trials for both NSCLC and MPM
patients. We discuss the rationale for combination immunotherapies for NSCLC and MPM
patients. Additionally, we have highlighted the challenges and strategies for overcoming
the obstacles facing translation of CAR T-cell therapy to solid tumors.
Abbreviations:
ACT (adoptive cell therapy), ADC (adenocarcinoma), ALK (anaplastic lymphoma kinase), CAF (cancer-associated fibroblast), CAR (chimeric antigen receptor), CEA (carcinoembryonic antigen), CTLA-4 (cytotoxic T-lymphocyte associated protein 4), DNR (dominant negative receptor), EGFR (epidermal growth factor receptor), FAP (fibroblast activation protein), FDA (Food and Drug Administration), GD2 (disialoganglioside), GPC3 (glypican-3), HER2 (human epidermal growth factor receptor 2), HLA (human leukocyte antigen), iCAR (inhibitory chimeric antigen receptor), iCasp9 (inducible caspase-9), IL (interleukin), MHC (major histocompatibility complex), MPM (malignant pleural mesothelioma), MSLN (mesothelin), MUC1 (mucin 1), NCI (National Cancer Institute), NSCLC (non-small cell lung cancer), PD-1 (programmed cell death protein 1), PD-L1 (programmed cell death-ligand 1), PGE2 (prostaglandin E2), ROR1 (receptor tyrosine-kinase-like orphan receptor), scFv (single-chain variable fragment), SCLC (small cell lung cancer), TAA (tumor-associated antigen), TAM (tumor-associated macrophage), TCR (T-cell receptor), TGFβ (transforming growth factor beta), TIL (tumor-infiltrating lymphocyte), TKI (tyrosine-kinase inhibitor), Treg (regulatory T-cell), VEGFR2 (vascular endothelial growth factor receptor 2)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: April 26, 2017
Accepted:
April 19,
2017
Received in revised form:
April 12,
2017
Received:
March 10,
2017
Identification
Copyright
© 2017 Elsevier Inc. All rights reserved.
