Immunotherapy of hepatocellular carcinoma using chimeric antigen receptors and bispecific antibodies

Cancer Lett. 2017 Jul 28:399:44-52. doi: 10.1016/j.canlet.2017.04.013. Epub 2017 Apr 17.

Abstract

Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide with an overall survival rate of less than 15% in developed countries. Despite attempts at new therapeutic strategies, the majority of patients succumb to this cancer. Buttressed by the highly successful clinical impact in melanoma, immunotherapy is gaining momentum as the next treatment modality for many human cancers. Chimeric antigen receptors (CAR) contain the antigen binding moieties of a monoclonal antibody and the co-stimulatory and signaling domains associated with effector receptor signaling. Bispecific antibodies (BsAb) combine the binding specificities of two different monoclonal antibodies, one activating a receptor on a killer effector cell, while the other engaging a tumor-associated antigen to initiate tumor cytotoxicity. In this review, we survey the HCC targets for which CARs and bispecific antibodies have been generated. The pros and cons of these targets for T-cell and Natural Killer cell based immunotherapy will be discussed.

Keywords: Bispecific antibody; Chimeric antigen receptor; Hepatocellular carcinoma; Treatment.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bispecific / adverse effects
  • Antibodies, Bispecific / therapeutic use*
  • Antibody Specificity
  • Antigens, Neoplasm / immunology*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / immunology
  • Carcinoma, Hepatocellular / pathology
  • Cell Death / drug effects
  • Cytotoxicity, Immunologic
  • Humans
  • Immunotherapy / adverse effects
  • Immunotherapy / methods*
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / immunology
  • Liver Neoplasms / pathology
  • Receptors, Antigen / immunology*
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / therapeutic use*
  • Signal Transduction / drug effects

Substances

  • Antibodies, Bispecific
  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Receptors, Antigen
  • Recombinant Fusion Proteins