title: Novel immunotherapies in lymphoid malignancies.
abstract: The success of the anti-CD20 monoclonal antibody rituximab in the treatment of lymphoid malignancies provided proof-of-principle for exploiting the immune system therapeutically. Since the FDA approval of rituximab in 1997, several novel strategies that harness the ability of T cells to target cancer cells have emerged. Reflecting on the promising clinical efficacy of these novel immunotherapy approaches, the FDA has recently granted 'breakthrough' designation to three novel treatments with distinct mechanisms. First, chimeric antigen receptor (CAR)-T-cell therapy is promising for the treatment of adult and paediatric relapsed and/or refractory acute lymphoblastic leukaemia (ALL). Second, blinatumomab, a bispecific T-cell engager (BiTE(®)) antibody, is now approved for the treatment of adults with Philadelphia-chromosome-negative relapsed and/or refractory B-precursor ALL. Finally, the monoclonal antibody nivolumab, which targets the PD-1 immune-checkpoint receptor with high affinity, is used for the treatment of Hodgkin lymphoma following treatment failure with autologous-stem-cell transplantation and brentuximab vedotin. Herein, we review the background and development of these three distinct immunotherapy platforms, address the scientific advances in understanding the mechanism of action of each therapy, and assess the current clinical knowledge of their efficacy and safety. We also discuss future strategies to improve these immunotherapies through enhanced engineering, biomarker selection, and mechanism-based combination regimens.
authors.affiliation: Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 330, New York, NY 10065, USA.
authors.forename: Connie Lee
authors.initials: CL
authors.lastname: Batlevi
authors.affiliation: Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 330, New York, NY 10065, USA.
authors.forename: Eri
authors.initials: E
authors.lastname: Matsuki
authors.affiliation: Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 330, New York, NY 10065, USA.
authors.forename: Renier J
authors.initials: RJ
authors.lastname: Brentjens
authors.affiliation: Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 330, New York, NY 10065, USA.
authors.forename: Anas
authors.initials: A
authors.lastname: Younes
mesh_terms: D000328:Adult; D018033:Antibodies, Bispecific / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000079963:Brentuximab Vedotin; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods*; D000077594:Nivolumab; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000276:immunology; D000069283:Rituximab / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D018796:Immunoconjugates; D000077594:Nivolumab; D000069283:Rituximab; C510808:blinatumomab; D000079963:Brentuximab Vedotin