Natural ligands and antibody-based fusion proteins: harnessing the immune system against cancer

Trends Mol Med. 2014 Feb;20(2):72-82. doi: 10.1016/j.molmed.2013.10.006. Epub 2013 Nov 19.


The insight that the immune system is able to eradicate tumor cells inspired the development of targeted immunotherapies. These novel approaches aim to trigger immune molecules and receptors, including CD3 on T cells and NKG2D and NKp30 on natural killer (NK) cells, to harness the immune system against cancer. In cancer patients, overcoming immune suppression induced by malignant cells or by the tumor microenvironment remains the major challenge to the clinical efficacy of immunotherapies. Recombinant constructs have been developed in various formats either utilizing natural ligands (immunoligands) or antibody-derived components (immunoconstructs) to circumvent mechanisms that counteract an effective antitumor immune response.

Keywords: NK cells; T cells; cancer; immunoconstructs; immunoligands; recombinant proteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies / pharmacology*
  • Antibodies / therapeutic use
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Humans
  • Immune System / drug effects
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Ligands*
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • NK Cell Lectin-Like Receptor Subfamily K / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / immunology
  • Receptors, IgG / metabolism
  • Receptors, Natural Cytotoxicity Triggering / metabolism
  • Recombinant Fusion Proteins / pharmacology*
  • Recombinant Fusion Proteins / therapeutic use
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology


  • Antibodies
  • Antineoplastic Agents
  • Ligands
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, IgG
  • Receptors, Natural Cytotoxicity Triggering
  • Recombinant Fusion Proteins