title: The cancer-immunity cycle as rational design for synthetic cancer drugs: Novel DC vaccines and CAR T-cells.
abstract: Cell therapy is an advanced form of cancer immunotherapy that has had remarkable clinical progress in the past decade in the search for cure of cancer. Most success has been achieved for chimeric antigen receptor (CAR) T-cells where CAR T-cells targeting CD19 show very high complete response rates for patients with refractory acute B-cell acute lymphoblastic leukemia (ALL) and are close to approval for this indication. CD19 CAR T-cells are also effective against B-cell chronic lymphoblastic leukemia (CLL) and B-cell lymphomas. Although encouraging, CAR T-cells have not yet proven clinically effective for solid tumors. This is mainly due to the lack of specific and homogenously expressed targets to direct the T-cells against and a hostile immunosuppressive tumor microenvironment in solid tumors. Cancer vaccines based on dendritic cells (DC) are also making progress although clinical efficacy is still lacking. The likelihood of success is however increasing now when individual tumors can be sequences and patient-specific neoepitopes identified. Neoepitopes and/or neoantigens can then be included in patient-based DC vaccines. This review discusses recent advancements of DC vaccines and CAR T-cells with emphasis on the cancer-immunity cycle, and current efforts to design novel cell therapies.
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Mohanraj
authors.initials: M
authors.lastname: Ramachandran
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Dimberg
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden. Electronic address: magnus.essand@igp.uu.se.
authors.forename: Magnus
authors.initials: M
authors.lastname: Essand
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology; D064987:Cell- and Tissue-Based Therapy; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D015195:Drug Design; D005818:Genetic Engineering; D015316:Genetic Therapy; D006801:Humans; D007109:Immunity / Q000187:drug effects* / Q000235:genetics; D056747:Immunomodulation / Q000187:drug effects / Q000235:genetics; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D059016:Tumor Microenvironment / Q000235:genetics / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D011948:Receptors, Antigen, T-Cell
keywords: CAR T-cells; Cancer immunotherapy; Cancer-immunity cycle; Dendritic cell vaccines; Gene therapy