Engineering anti-tumor monoclonal antibodies and fc receptors to enhance ADCC by human NK cells

Kate J. Dixon, Jianming Wu, Bruce Walcheck

Research output: Contribution to journalReview articlepeer-review

Abstract

Tumor-targeting monoclonal antibodies (mAbs) are the most widely used and characterized immunotherapy for hematologic and solid tumors. The significance of this therapy is their direct and indirect effects on tumor cells, facilitated by the antibody’s antigen-binding fragment (Fab) and fragment crystallizable region (Fc region), respectively. The Fab can modulate the function of cell surface markers on tumor cells in an agonistic or antagonistic manner, whereas the Fc region can be recognized by an Fc receptor (FcR) on leukocytes through which various effector functions, including antibody-dependent cell-mediated cytotoxicity (ADCC), can be elicited. This process is a key cytolytic mechanism of natural killer (NK) cells. These innate lymphocytes in the human body recognize tumor-bound antibodies exclusively by the IgG Fc receptor CD16A (FcγIIIA). Two allelic versions of CD16A bind IgG with either lower or higher affinity. Cancer patients homozygous for the higher affinity allele of CD16A have been reported to respond significantly better to mAb therapies for various malignancies. These studies revealed that mAb therapy efficacy positively correlates with higher affinity binding to CD16A. Approaches to enhance tumor antigen targeting by NK cells by modifying the Fc portion of antibodies or the FcR on NK cells are the focus of this review.

Original languageEnglish (US)
Article number312
Pages (from-to)1-13
Number of pages13
JournalCancers
Volume13
Issue number2
DOIs
StatePublished - Jan 2 2021

Bibliographical note

Funding Information:
Funding: Research in the authors’ laboratory is funded by the National Institutes of Health, including the grant R01CA203348, R21AI149395, and by the Lymphoma Research Foundation.

Publisher Copyright:
© 2021 by the authors.

Keywords

  • ADCC
  • CD16
  • FcR
  • Glycoengineering
  • Monoclonal antibodies
  • NK cell

PubMed: MeSH publication types

  • Journal Article
  • Review

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