Bispecific antibodies and CARs: generalized immunotherapeutics harnessing T cell redirection

Curr Opin Immunol. 2016 Jun;40:24-35. doi: 10.1016/j.coi.2016.02.006. Epub 2016 Mar 8.


To realize the full potential of cancer immunotherapy, the latest generation immunotherapeutics are designed to harness the potent tumor-killing capacity of T cells. Thus, to mobilize T cells, new optimized bispecific antibody (BsAb) designs, enabling efficient polyclonal redirection of cytotoxic activity through binding to CD3 and a Tumor Associated Antigen (TAA) and refined genetically modified T cells have recently expanded the arsenal of available options for cancer treatment. This review presents the current understanding of the parameters crucial to the design of optimal T cell redirecting BsAb and chimeric antigen receptor (CAR)-modified T cells. However, there are additional questions that require thorough elucidation. Both modalities will benefit from design changes that may increase the therapeutic window. One such approach could employ the discrimination afforded by multiple TAA to significantly increase selectivity.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Bispecific / therapeutic use*
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / metabolism
  • CD3 Complex / immunology
  • CD3 Complex / metabolism
  • Cancer Vaccines / immunology*
  • Cytotoxicity, Immunologic
  • Genetic Therapy
  • Humans
  • Immunotherapy / methods*
  • Lymphocyte Activation
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell / metabolism
  • Recombinant Fusion Proteins / genetics*
  • Recombinant Fusion Proteins / metabolism
  • T-Lymphocytes / physiology*
  • T-Lymphocytes / transplantation


  • Antibodies, Bispecific
  • Antigens, Neoplasm
  • CD3 Complex
  • Cancer Vaccines
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins