High-affinity CD16-polymorphism and Fc-engineered antibodies enable activity of CD16-chimeric antigen receptor-modified T cells for cancer therapy

Br J Cancer. 2019 Jan;120(1):79-87. doi: 10.1038/s41416-018-0341-1. Epub 2018 Nov 15.


Background: CD16-chimeric antigen receptors (CAR) T cells recognise the Fc-portion of therapeutic antibodies, which can enable the selective targeting of different antigens. Limited evidence exists as to which CD16-CAR design and antibody partner might be most effective. We have hypothesised that the use of high-affinity CD16 variants, with increased Fc-terminus antibody affinity, combined with Fc-engineered antibodies, would provide superior CD16-CAR T cell efficacy.

Methods: CD16-CAR T (wild-type or variants) cells were co-cultured with Panc-1 pancreatic cancer, Raji lymphoma or A375 melanoma cells in the presence or absence of anti-CD20, anti-MCSP, wild-type or the glycoengineered antibody variants. The endpoints were proliferation, activation, and cytotoxicity in vitro.

Results: The CD16 158 V variant of CD16-CAR T cells showed increased cytotoxic activity against all the tested cancer cells in the presence of the wild-type antibody directed against MCSP or CD20. Glycoengineered antibodies enhanced CD16-CAR T cell activity irrespective of CD16 polymorphisms as compared with the wild-type antibody. The combination of the glycoengineered antibodies with the CD16-CAR 158 V variant synergised as seen by the increase in all endpoints.

Conclusion: These results indicate that CD16-CAR with the high-affinity CD16 variant 158 V, combined with Fc-engineered antibodies, have high anti-tumour efficacy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / pharmacology
  • Antibody-Dependent Cell Cytotoxicity / genetics
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • ErbB Receptors / genetics
  • Humans
  • Immunoglobulin Fc Fragments / genetics
  • Immunoglobulin Fc Fragments / pharmacology
  • Immunotherapy*
  • Immunotherapy, Adoptive*
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Mice
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Polymorphism, Genetic
  • Receptors, Chimeric Antigen / immunology*
  • Receptors, Chimeric Antigen / therapeutic use
  • Receptors, IgG / immunology
  • Rituximab / pharmacology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology


  • Antibodies, Monoclonal
  • Immunoglobulin Fc Fragments
  • Receptors, Chimeric Antigen
  • Receptors, IgG
  • Rituximab
  • EGFR protein, human
  • ErbB Receptors