Combination immune therapies to enhance anti-tumor responses by NK cells

Ashley Mentlik James, Adam D. Cohen, Kerry S. Campbell

Research output: Contribution to journalReview articlepeer-review

66 Scopus citations

Abstract

Natural killer (NK) cells are critical innate immune lymphocytes capable of destroying virally infected or cancerous cells through targeted cytotoxicity and further assisting in the immune response by releasing inflammatory cytokines. NK cells are thought to contribute to the process of tumor killing by certain therapeutic monoclonal antibodies (mAb) by directing antibody-dependent cellular cytotoxicity (ADCC) through FcγRIIIA (CD16). Numerous therapeutic mAb have been developed that target distinct cancer-specific cell markers and may direct NK cell-mediated ADCC. Recent therapeutic approaches have combined some of these cancer-specific mAb with additional strategies to optimize NK cell cytotoxicity. These include agonistic mAb targeting NK cell activating receptors and mAbs blocking NK cell inhibitory receptors to enhance NK cell functions. Furthermore, several drugs that can potentiate NK cell cytotoxicity through other mechanisms are being used in combination with therapeutic mAb. In this review, we examine the mechanisms employed by several promising agents used in combination therapies that enhance natural or Ab-dependent cytotoxicity of cancer cells by NK cells, with a focus on treatments for leukemia and multiple myeloma.

Original languageEnglish
Article numberArticle 481
Pages (from-to)481
JournalFrontiers in Immunology
Volume4
Issue numberDEC
DOIs
StatePublished - 2013

Keywords

  • ADCC
  • Antibodies
  • Immunotherapy of cancer
  • Monoclonal
  • Multiple myeloma
  • NK cells

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