title: Chimeric antigen receptor-modified T cells for the treatment of solid tumors: Defining the challenges and next steps.
abstract: Chimeric antigen receptor (CAR) T cell therapy has shown promise in CD19 expressing hematologic malignancies, but how to translate this success to solid malignancies remains elusive. Effective translation of CAR T cells to solid tumors will require an understanding of potential therapeutic barriers, including factors that regulate CAR T cells expansion, persistence, trafficking, and fate within tumors. Herein, we describe the current state of CAR T cells in solid tumors; define key barriers to CAR T cell efficacy and mechanisms underlying these barriers, outline potential avenues for overcoming these therapeutic obstacles, and discuss the future of translating CAR T cells for the treatment of patients with solid malignancies.
authors.affiliation: Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: gregory.beatty@uphs.upenn.edu.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Beatty
authors.affiliation: Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: O'Hara
mesh_terms: D000818:Animals; D058851:GPI-Linked Proteins / Q000276:immunology; D041722:Genes, Transgenic, Suicide / Q000502:physiology; D018773:Genes, erbB-1 / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000379:methods*; D000090204:Mesothelin; D009369:Neoplasms / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000627:therapeutic use*; D059016:Tumor Microenvironment
chemical_list: D058851:GPI-Linked Proteins; D011948:Receptors, Antigen, T-Cell; D000090204:Mesothelin
keywords: CAR T cells; Cellular immunity; Chimeric antigen receptor; Solid malignancies; Tumor microenvironment