Chimeric Antigen Receptor Engineering: A Right Step in the Evolution of Adoptive Cellular Immunotherapy

Abstract

Cancer immunotherapy comprises different therapeutic strategies that exploit the use of distinct components of the immune system, with the common goal of specifically targeting and eradicating neoplastic cells. These varied approaches include the use of specific monoclonal antibodies, checkpoint inhibitors, cytokines, therapeutic cancer vaccines and cellular anticancer strategies such as activated dendritic cell (DC) vaccines, tumor-infiltrating lymphocytes (TILs) and, more recently, genetically engineered T cells. Each one of these approaches has demonstrated promise, but their generalized success has been hindered by the paucity of specific tumor targets resulting in suboptimal tumor responses and unpredictable toxicities. This review will concentrate on recent advances on the use of engineered T cells for adoptive cellular immunotherapy (ACI) in cancer.

Keywords: :

• chimeric antigen receptors
• cancer testis antigens
• immunotherapy
• cancer stem cells

Abbreviations:

• AAV: adeno-associated virus
• Ad: adenovirus
• ACI: adoptive cellular immunotherapy
• AKAP4: A-kinase anchoring protein 4
• ALL: acute lymphoblastic leukemia
• AlloSCT: allogeneic stem cell transplant
• AML: acute myeloid leukemia
• ASP: AKAP-associated sperm protein
• CAIX: carbonic anhydrase-IX
• CAR: chimeric antigen receptor
• CAReTC: chimeric antigen receptor-engineered T cell
• CEA: carcinoembryonic antigen
• CLL: chronic lymphocytic leukemia
• CTA: cancer testis antigen
• CTL: cytotoxic T lymphocyte
• DC: dendritic cell
• EBV: Epstein–Bar virus
• ERK: extracellular signal-regulated kinase
• FAP: fibroblast activation protein
• FITC: fluorescein isothiocyanate
• GVHD: graft-vs.-host disease
• HAMA: human anti-mouse antibodies
• HLA: human leukocyte antigen
• HSV: herpes simplex virus
• HSCT: hematopoietic stem cell transplant
• HvG: host versus graft
• IL-1, IL-2: interleukin-1, interleukin-2
• ITR: inverted terminal repeat
• JNK: c-Jun N-terminal kinase
• LAK: lymphokine activated killer cell
• Ly-CM: lymphocyte-conditioned medium
• MHC: major histocompatibility complex
• NFAT: nuclear factor of activated T cell
• NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells
• NK: natural killer
• NKG2D: natural killer receptor G2D
• NHL: Non-Hodgkin's lymphoma
• PD-1: programmed death-1
• PKA: protein A-kinase
• rAAV: recombinant AAV
• SIRS: systemic inflammatory response syndrome
• SP17: sperm protein 17
• scFv: single-chain variable fragment
• TAA: tumor-associating antigen
• T_CM: central memory T cell
• TCR: T-cell receptors
• T_E: effector T cell
• T_EM: effector memory T cell
• T_H: helper T cell
• TIL: tumor-infiltrating lymphocyte
• TNF: tumor necrosis factor
• TRAF: TNF receptor-associated factor
• TRUCK: T cells redirected for universal cytokine killing
• T_reg: regulatory T cell
• T_SCM: stem cell memory T cell