title: 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.
authors.affiliation: Division of Hematology and Oncology, Texas Tech University Health Sciences Center , Lubbock, TX , USA.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Figueroa
authors.forename: Adair
authors.initials: A
authors.lastname: Reidy
authors.forename: Leonardo
authors.initials: L
authors.lastname: Mirandola
authors.forename: Kayley
authors.initials: K
authors.lastname: Trotter
authors.forename: Natallia
authors.initials: N
authors.lastname: Suvorava
authors.forename: Alejandro
authors.initials: A
authors.lastname: Figueroa
authors.forename: Venu
authors.initials: V
authors.lastname: Konala
authors.forename: Amardeep
authors.initials: A
authors.lastname: Aulakh
authors.forename: Lauren
authors.initials: L
authors.lastname: Littlefield
authors.forename: Fabio
authors.initials: F
authors.lastname: Grizzi
authors.forename: Rakhshanda Layeequr
authors.initials: RL
authors.lastname: Rahman
authors.forename: Marjorie R
authors.initials: MR
authors.lastname: Jenkins
authors.forename: Breeanna
authors.initials: B
authors.lastname: Musgrove
authors.forename: Saba
authors.initials: S
authors.lastname: Radhi
authors.forename: Nicholas
authors.initials: N
authors.lastname: D'Cunha
authors.forename: Luke N
authors.initials: LN
authors.lastname: D'Cunha
authors.forename: Paul L
authors.initials: PL
authors.lastname: Hermonat
authors.forename: Everardo
authors.initials: E
authors.lastname: Cobos
authors.forename: Maurizio
authors.initials: M
authors.lastname: Chiriva-Internati
mesh_terms: D000818:Animals; D005818:Genetic Engineering; D006801:Humans; D016219:Immunotherapy, Adoptive; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D013601:T-Lymphocytes / Q000502:physiology* / Q000637:transplantation
chemical_list: D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins
keywords: AAV: adeno-associated virus; ACI: adoptive cellular immunotherapy; AKAP4: A-kinase anchoring protein 4; ALL: acute lymphoblastic leukemia; AML: acute myeloid leukemia; ASP: AKAP-associated sperm protein; Ad: adenovirus; AlloSCT: allogeneic stem cell transplant; 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; HSCT: hematopoietic stem cell transplant; HSV: herpes simplex virus; 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; 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; SIRS: systemic inflammatory response syndrome; SP17: sperm protein 17; TAA: tumor-associating antigen; TCM: central memory T cell; TCR: T-cell receptors; TE: effector T cell; TEM: effector memory T cell; TH: helper T cell; TIL: tumor-infiltrating lymphocyte; TNF: tumor necrosis factor; TRAF: TNF receptor-associated factor; TRUCK: T cells redirected for universal cytokine killing; TSCM: stem cell memory T cell; Treg: regulatory T cell; cancer stem cells; cancer testis antigens; chimeric antigen receptors; immunotherapy; rAAV: recombinant AAV; scFv: single-chain variable fragment