Investigational therapies targeting lymphocyte antigens for the treatment of non-Hodgkin's lymphoma

Expert Opin Investig Drugs. 2015;24(7):897-912. doi: 10.1517/13543784.2015.1038342. Epub 2015 Apr 21.

Abstract

Introduction: The advent of the anti-CD20 mAb rituximab has opened a new era in the treatment of non-Hodgkin's lymphomas (NHL), markedly altering standard treatment strategies. Moreover, the proof-of-concept that targeting a specific lymphocyte surface antigen may induce a highly effective and safe targeted killing of malignant cells has opened the door to the development of a plethora of novel mAbs directed towards different B- and T-cell-specific antigens.

Areas covered: This review discusses the recent available clinical data about new-generation anti-CD20 mAbs characterized by increased antibody- (obinutuzumab) or complement-dependent cyotoxicity (ofatumumab) as well as novel investigational agents targeting other lymphocyte antigens (e.g., CD19, CD22, CD30, CD40, CD52, CCR4), which are currently under investigation for B- and T-cell NHL treatment. In addition, antibody-drug conjugates (inotuzumab ozogamicin, brentuximab vedotin, polatuzumab vedotin), bispecific T-cell engagers (blinatumomab) and a new class of antibodies targeting cytotoxic T-lymphocyte-associated antigen 4, programmed death 1 or programmed death ligand 1 (immune checkpoint inhibitors) are specifically considered.

Expert opinion: Among the novel mAbs challenging rituximab, obinutuzumab seems to be in the most advanced phase, with the results of randomized trials awaited shortly. Brentuximab vedotin is increasing its role in T-cell NHL. Furthermore, immune checkpoint inhibitors have the potential to acquire a great relevance in NHL therapy.

Keywords: CD20; CD30; CTLA-4; PD-1; PD-L1; antibody–drug conjugates; bispecific T-cell engagers; immune checkpoint inhibitors; mAb; non-Hodgkin’s lymphoma.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antigens, Surface / immunology*
  • Antineoplastic Agents / therapeutic use*
  • Humans
  • Immunoconjugates / therapeutic use
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Lymphoma, Non-Hodgkin / immunology
  • T-Lymphocytes / immunology
  • Therapies, Investigational

Substances

  • Antibodies, Monoclonal
  • Antigens, Surface
  • Antineoplastic Agents
  • Immunoconjugates