title: Clinical pharmacology of CAR-T cells: Linking cellular pharmacodynamics to pharmacokinetics and antitumor effects.
abstract: Adoptive cell transfer of T cells genetically modified with tumor-reactive chimeric antigen receptors (CARs) is a rapidly emerging field in oncology, which in preliminary clinical trials has already shown striking antitumor efficacy. Despite these premises, there are still a number of open issues related to CAR-T cells, spanning from their exact mechanism of action (pharmacodynamics), to the factors associated with their in vivo persistence (pharmacokinetics), and, finally, to the relative contribution of each of the two in determining the antitumor effects and accompanying toxicities. In light of the unprecedented curative potential of CAR-T cells and of their predicted wide availability in the next few years, in this review we will summarize the current knowledge on the clinical pharmacology aspects of what is anticipated to be a brand new class of biopharmaceuticals to join the therapeutic armamentarium of cancer doctors.
authors.affiliation: Innovative Immunotherapies Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Hospital Scientific Institute, Milano, Italy; Vita-Salute San Raffaele University, Milano, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Norelli
authors.affiliation: Innovative Immunotherapies Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Hospital Scientific Institute, Milano, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Casucci
authors.affiliation: Vita-Salute San Raffaele University, Milano, Italy; Experimental Hematology Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Hospital Scientific Institute, Milano, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Bonini
authors.affiliation: Innovative Immunotherapies Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Hospital Scientific Institute, Milano, Italy; Vita-Salute San Raffaele University, Milano, Italy. Electronic address: bondanza.attilio@hsr.it.
authors.forename: A
authors.initials: A
authors.lastname: Bondanza
mesh_terms: D006801:Humans; D016219:Immunotherapy, Adoptive; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: C000605956:CD19-specific chimeric antigen receptor; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins
keywords: Adoptive cell transfer; Cancer immunotherapy; Clinical results; Genetically modified T cells; Pharmacokinetics/pharmacodynamics; Toxicities