Bispecific antibody based therapeutics: Strengths and challenges

Blood Rev. 2018 Jul;32(4):339-347. doi: 10.1016/j.blre.2018.02.004. Epub 2018 Feb 20.

Abstract

Monoclonal antibody-based targeted therapy has greatly improved treatment options for patients. However, long-term efficacy of such antibodies is limited by resistance mechanisms. New insights into the mechanisms by which tumors evade immune control have driven innovative therapeutic strategies to eliminate cancer by re-directing immune cells to tumors. Advances in protein engineering technology have generated multiple bispecific antibody (BsAb) formats capable of targeting multiple antigens as a single agent. Approval of two BsAb and three check point blocking mAbs represent a paradigm shift in the use of antibody constructs. Since BsAbs can directly target immune cells to tumors, drug resistance and severe adverse effects are much reduced. The wave of next generation "bispecific or multispecific antibodies" has advanced multiple candidates into ongoing clinical trials. In this review, we focus on preclinical and clinical studies in hematological malignancies as well as discuss reasons for the limited success of BsAbs against solid tumors.

Keywords: Activated T cells; Bispecific antibody; Immunotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antibodies, Bispecific / pharmacology
  • Antibodies, Bispecific / therapeutic use*
  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Hematologic Neoplasms / drug therapy
  • Hematologic Neoplasms / pathology
  • Humans
  • Immunoglobulin G / pharmacology
  • Immunoglobulin G / therapeutic use
  • Immunotherapy / methods
  • Molecular Targeted Therapy
  • Tumor Escape / drug effects
  • Tumor Escape / immunology
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology

Substances

  • Antibodies, Bispecific
  • Antineoplastic Agents, Immunological
  • Immunoglobulin G