[Recombinant Monoclonal Antibodies, From Tumor Targeting to Cancer Immunotherapy: A Critical Overview]

Mol Biol (Mosk). Nov-Dec 2017;51(6):1024-1038. doi: 10.7868/S0026898417060131.
[Article in Russian]

Abstract

In view of the explosion of the present clinical use of monoclonal antibodies (mAbs), not only in the treatment of cancer, but also of autoimmune diseases, I was asked to review the development of mAbs in tumor diagnosis and therapy, with some illustrations of our own contribution in the field. The initial use of radiolabeled mAbs for tumor targeting and radioimmunotherapy led to the extensive clinical application of unlabeled, "humanized" mAbs for cancer therapy, which I describe with a critical perspective. The introduction of recombinant bispecific antibodies, capable of bridging T lymphocytes with tumor cells and inducing killing of the cancer cells, was found to be mostly active in the treatment of hematological malignancies. Most interestingly, the use of mAbs not directed to the tumor cells, but to inhibitory receptors expressed by cytotoxic T lymphocytes, which trigger them to kill the cancer cells, represents a new form of active cancer immunotherapy. My motivation in writing this review was related to my long-term interactions with several Russian scientists, mentioned at the end of this article.

Keywords: antibodies; bispecific; carcinoembryonic antigen; immunotherapy; rituximab; аnti-tumor antibodies.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Bispecific / biosynthesis
  • Antibodies, Bispecific / pharmacology
  • Antibodies, Monoclonal / biosynthesis
  • Antibodies, Monoclonal / pharmacology*
  • Carcinoembryonic Antigen / chemistry
  • Carcinoembryonic Antigen / genetics
  • Carcinoembryonic Antigen / immunology*
  • Cell Engineering
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / therapy*
  • Cytotoxicity, Immunologic
  • Gene Expression
  • Hematologic Neoplasms / genetics
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / pathology
  • Hematologic Neoplasms / therapy*
  • Humans
  • Immunotherapy / methods*
  • Iodine Radioisotopes
  • Mice
  • Receptors, Antigen, T-Cell / chemistry
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Staining and Labeling / methods
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Bispecific
  • Antibodies, Monoclonal
  • Carcinoembryonic Antigen
  • Iodine Radioisotopes
  • Receptors, Antigen, T-Cell
  • Recombinant Proteins