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

• Published in: International Reviews of Immunology Vol. 34; no. 2; pp. 154 - 187
• Main Authors: Figueroa, Jose A., Reidy, Adair, Mirandola, Leonardo, Trotter, Kayley, Suvorava, Natallia, Figueroa, Alejandro, Konala, Venu, Aulakh, Amardeep, Littlefield, Lauren, Grizzi, Fabio, Rahman, Rakhshanda Layeequr, R. Jenkins, Marjorie, Musgrove, Breeanna, Radhi, Saba, D'Cunha, Nicholas, D'Cunha, Luke N., Hermonat, Paul L., Cobos, Everardo, Chiriva-Internati, Maurizio
• Format: Journal Article
• Language: English
• Published: New York Informa Healthcare 04.03.2015
• Subjects: AAV: adeno-associated virus; ACI: adoptive cellular immunotherapy; Ad: adenovirus; AKAP4: A-kinase anchoring protein 4; ALL: acute lymphoblastic leukemia; AlloSCT: allogeneic stem cell transplant; AML: acute myeloid leukemia; Animals; ASP: AKAP-associated sperm protein; CAIX: carbonic anhydrase-IX; cancer stem cells; cancer testis antigens; CAR: chimeric antigen receptor; CAReTC: chimeric antigen receptor-engineered T cell; CEA: carcinoembryonic antigen; central memory T cell; chimeric antigen receptors; CLL: chronic lymphocytic leukemia; CTA: cancer testis antigen; CTL: cytotoxic T lymphocyte; DC: dendritic cell; EBV: Epstein-Bar virus; effector memory T cell; effector T cell; ERK: extracellular signal-regulated kinase; FAP: fibroblast activation protein; FITC: fluorescein isothiocyanate; Genetic Engineering; GVHD: graft-vs.-host disease; HAMA: human anti-mouse antibodies; helper T cell; HLA: human leukocyte antigen; HSCT: hematopoietic stem cell transplant; HSV: herpes simplex virus; Humans; HvG: host versus graft; IL-1, IL-2: interleukin-1, interleukin-2; immunotherapy; Immunotherapy, Adoptive; ITR: inverted terminal repeat; JNK: c-Jun N-terminal kinase; LAK: lymphokine activated killer cell; Ly-CM: lymphocyte-conditioned medium; MHC: major histocompatibility complex; Neoplasms - immunology; Neoplasms - therapy; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; NFAT: nuclear factor of activated T cell; NHL: Non-Hodgkin's lymphoma; NK: natural killer; NKG2D: natural killer receptor G2D; PD-1: programmed death-1; PKA: protein A-kinase; rAAV: recombinant AAV; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - metabolism; Recombinant Fusion Proteins - genetics; reg; regulatory T cell; scFv: single-chain variable fragment; SCM; SIRS: systemic inflammatory response syndrome; SP17: sperm protein 17; stem cell memory T cell; T-Lymphocytes - physiology; T-Lymphocytes - transplantation; TAA: tumor-associating antigen; TCR: T-cell receptors; TIL: tumor-infiltrating lymphocyte; TNF: tumor necrosis factor; TRAF: TNF receptor-associated factor; TRUCK: T cells redirected for universal cytokine killing; ALL: acute lymphoblastic leukemia; HvG: host versus graft; TE: effector T cell; CLL: chronic lymphocytic leukemia; DC: dendritic cell; GVHD: graft-vs.-host disease; NFAT: nuclear factor of activated T cell; ACI: adoptive cellular immunotherapy; FITC: fluorescein isothiocyanate; HSV: herpes simplex virus; cancer testis antigens; Ad: adenovirus; Ly-CM: lymphocyte-conditioned medium; TIL: tumor-infiltrating lymphocyte; TEM: effector memory T cell; IL-1, IL-2: interleukin-1, interleukin-2; TCM: central memory T cell; HLA: human leukocyte antigen; CTA: cancer testis antigen; AKAP4: A-kinase anchoring protein 4; AlloSCT: allogeneic stem cell transplant; AAV: adeno-associated virus; CAReTC: chimeric antigen receptor-engineered T cell; ITR: inverted terminal repeat; CTL: cytotoxic T lymphocyte; TCR: T-cell receptors; TRAF: TNF receptor-associated factor; AML: acute myeloid leukemia; TRUCK: T cells redirected for universal cytokine killing; TSCM: stem cell memory T cell; TAA: tumor-associating antigen; scFv: single-chain variable fragment; ERK: extracellular signal-regulated kinase; CAR: chimeric antigen receptor; FAP: fibroblast activation protein; EBV: Epstein–Bar virus; immunotherapy; rAAV: recombinant AAV; ASP: AKAP-associated sperm protein; CEA: carcinoembryonic antigen; cancer stem cells; CAIX: carbonic anhydrase-IX; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; NK: natural killer; SIRS: systemic inflammatory response syndrome; SP17: sperm protein 17; Treg: regulatory T cell; MHC: major histocompatibility complex; PKA: protein A-kinase; TH: helper T cell; HAMA: human anti-mouse antibodies; HSCT: hematopoietic stem cell transplant; NKG2D: natural killer receptor G2D; LAK: lymphokine activated killer cell; JNK: c-Jun N-terminal kinase; PD-1: programmed death-1; chimeric antigen receptors; NHL: Non-Hodgkin's lymphoma; TNF: tumor necrosis factor
• ISSN: 0883-0185; 1937-4364; 1563-5244
• DOI: 10.3109/08830185.2015.1018419

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.