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CAR T-cell therapy for lung cancer and malignant pleural mesothelioma

  • Masha Zeltsman
    Affiliations
    Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
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  • Jordan Dozier
    Affiliations
    Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
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  • Erin McGee
    Affiliations
    Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
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  • Daniel Ngai
    Affiliations
    Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
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  • Prasad S. Adusumilli
    Correspondence
    Reprint requests: Prasad S. Adusumilli, Deputy Chief, Translational and Clinical Research, Thoracic Service, Department of Surgery, Associate Attending, Thoracic Service, Department of Surgery, Member, Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065
    Affiliations
    Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY

    Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY
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Published:April 26, 2017DOI:https://doi.org/10.1016/j.trsl.2017.04.004
      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)
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