Development of cellular and humoral immunotherapy to multiple myeloma based on the NKG2A-HLAE immune checkpoint

  • Dye, Gregory (CoPI)
  • Kay, Richard (CoPI)
  • Boyer, Douglas M. (CoPI)
  • Borths, Matthew R. (PI)
  • Porgador, Angel (PI)
  • Campbell, Kerry (CoPI)

Project Details

Description

Natural killer (NK) cells are normal white blood cells of the innate immune system that play an important role in attack of multiple myeloma (MM) tumor cells, especially in early stages of disease. Despite some improved overall survival using newly developed immunotherapeutic agents over the past decade, MM remains an essentially incurable disease, and new therapies are needed. Most normal cells in the body express a surface molecule called HLA-E that serves as a marker to prevent the innate immune natural killer (NK) cells from attacking. The NKGZA receptor on NK cells recognizes HLA-E with a specific peptide attached, and this interaction sends an inhibitory signal into the NK cell that impedes targeted killing responses toward the HLA-E+peptide-bearing cell. We recently developed an anti-HLA-E antibody that blocks NKGZA recognition of HLA-E+peptide, which Could be a l.lSCfi1l therapeutic to restore NK cell responses toward HLA-E-expressing tumors. Experiments in this proposal will explore the role of the HLA-E-l-peptide interaction in repressing NK cell responses toward MM and the effectiveness of our anti-HLA-E+peptide antibody in restoring NK cell responses. We expect to accumulate preclinical evidence demonstrating that antibody-mediated blockade of the HLA-E+peptide/NKGZA interaction can promote NK cell responses toward myeloma. Such evidence could potentially support a future clinical trial to test anti-HLA-E+peptide antibody as a novel immunotherapeutic agent to treat MM patients.

StatusActive
Effective start/end date1/07/2130/06/25

Funding

  • United States-Israel Binational Science Foundation (BSF)

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