title: Prospects to improve chimeric antigen receptor T-cell therapy for solid tumors.
abstract: Adoptive transfer of patient-derived T-cells engineered with a chimeric antigen receptor (CAR) targeting the pan-B-cell marker CD19 has led to complete remission in patients with B-cell leukemias while response rates are more modest for B-cell lymphomas. This can be attributed to the fact that the semi-solid structure of lymphomas impedes T-cell infiltration and that the immune suppressive microenvironment within these tumors dampens the effect of CAR T-cells. These obstacles are even more pronounced for solid tumors where dense and often highly immunosuppressive structures are found. This article focuses on different aspects of how to improve CAR T-cells for solid tumors, primarily by decreasing their sensitivity to the harsh tumor microenvironment, by altering the immunosuppressive microenvironment inside tumors and by inducing bystander immunity.
authors.affiliation: Department of Immunology, Genetics & Pathology, Science for Life Laboratory, Uppsala University, SE-75185 Uppsala, Sweden.
authors.forename: Chuan
authors.initials: C
authors.lastname: Jin
authors.affiliation: Department of Immunology, Genetics & Pathology, Science for Life Laboratory, Uppsala University, SE-75185 Uppsala, Sweden.
authors.forename: Di
authors.initials: D
authors.lastname: Yu
authors.affiliation: Department of Immunology, Genetics & Pathology, Science for Life Laboratory, Uppsala University, SE-75185 Uppsala, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Essand
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods* / Q000639:trends; 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; D019139:Tumor Escape; D059016:Tumor Microenvironment
chemical_list: D018941:Antigens, CD19; D019496:Cancer Vaccines; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins
keywords: CAR T-cells; bystander immunity; immune suppression