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03-11-2015 | Hematologic cancers | Article

Novel immunotherapies in lymphoid malignancies

Connie Lee Batlevi, Eri Matsuki, Renier J. Brentjens, Anas Younes


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.

Nat Rev Clin Oncol 2016; 13: 25–40. doi:10.1038/nrclinonc.2015.187

Subject terms: Cancer immunotherapy • Lymphoma

The concept of immunotherapy for treating cancer emerged almost a century ago; the graft-versus-tumour effect following allogeneic haematopoietic-stem-cell transplantation (HSCT) was one of the first examples of immunotherapy.1 Furthermore, the success of rituximab in treating lymphoid malignancies provided proof-of-principle for exploiting the immune system in a target-specific manner.2, 3, 4 With improved technology and a better understanding of immune-regulatory mechanisms, cancer immunotherapy is rapidly evolving to exploit the therapeutic value of activating autologous T cells.

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