Strategies to Enhance Migration and Persistence of Chimeric Antigen Receptor (CAR)-T Cells into Tumors
Since the past few decades, immunotherapy based on the adoptive transfer of tumor-specific T-cells is providing a promising form of cancer treatment. This result has been obtained through the improvement of the methodologies used to expand ex vivo antigen
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Strategies to Enhance Migration and Persistence of Chimeric Antigen Receptor (CAR)-T Cells into Tumors Yuhui Chen, Gianpietro Dotti, and Barbara Savoldo
Abstract Since the past few decades, immunotherapy based on the adoptive transfer of tumor-specific T-cells is providing a promising form of cancer treatment. This result has been obtained through the improvement of the methodologies used to expand ex vivo antigen-specific T cells, and through technology advancements in T-cell engineering aimed at transferring into these cells chimeric antigen receptors (CAR) or αβTCRs chains. High enthusiasm is especially directed to the CAR technology, as this confers MHC-independent antigen-specificity to T cells, thus allowing broad clinical applications. The greatest advances have been achieved in lymphoid malignancies, while the clinical benefits of CAR-T cells to solid tumors still remain uncertain. In this review we will explore two of the problems that are currently perceived as limiting the success of the clinical translation of CAR-T cells in solid tumors: namely, the recruitment and survival of tumor-specific T cells in the microenvironment. Keywords Chimeric antigen receptor • Immunotherapy • Chemokines • Migration and Infiltration • Improving Persistence • Overcoming immune-evasion
Y. Chen Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA G. Dotti Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA B. Savoldo (*) Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA Department of Pediatrics, University of North Carolina, Chapel Hill, NC, USA e-mail: [email protected] © Springer International Publishing Switzerland 2016 E. Donnadieu (ed.), Defects in T Cell Trafficking and Resistance to Cancer Immunotherapy, Resistance to Targeted Anti-Cancer Therapeutics 9, DOI 10.1007/978-3-319-42223-7_8
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Abbreviations Bcl-2 Bcl-xL CAR CD CTLA4 DPP4 ECM ERK GD2 GM-CSF Gro-α HVEM IDO IFN IL LAG3 M2 MDC MHC MDSC NF-kB NKGD2 PD1 PD-L1/PD-L2 PGs RANTES ROS siRNA TARC TCR Tregs
8.1
B-cell lymphoma 2 B-cell lymphoma-extra large Chimeric antigen receptor Cluster of Differentiation Cytotoxic T-lymphocyte-associated protein 4 Dipeptidyl peptidase 4 Extra cellular matrix Extracellular signal-regulated kinases Ganglioside Diasialo 2 Granulocyte-macrophage colony-stimulating factor Growth-regulated oncogene-α Herpes Virus Entry Mediator Indoleamine 2, 3-dioxygenase Interferon Interleukin Lymphocyte-activation gene 3 Macrophages type 2 Macrophage-derived chemokine major histocompatibility complex Myeloid derived suppressor cells Nuclear factor-kB Natural Killer Group 2D Programmed cell death protein 1 Programmed death-ligand 1/2 Proteoglycans Regulated on Activation, Normal T Cell Expressed and Secreted Reactive oxygen species Small interfering RNA Thymus and activation-regulated chemokine T cell receptor Regula
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