The Monoclonal Antibody NEO-201 Enhances Natural Killer Cell Cytotoxicity Against Tumor Cells Through Blockade of the

Massimo Fantini1, Justin M David1, Christina M Annunziata2

  • 1Precision Biologics, Inc., Bethesda, Maryland.

Insights

NEO-201 antibody blocks the interaction between CEACAM5 on tumor cells and CEACAM1 on natural killer (NK) cells. This blockade restores NK cell

Area of Science:

  • Immunology
  • Oncology
  • Cell Biology

Background:

  • Natural killer (NK) cells are crucial for innate immunity and cancer surveillance.
  • The interaction between carcinoembryonic antigen (CEA) on tumor cells and CEACAM1 on NK cells inhibits NK cell anti-tumor activity.
  • CEACAM1 is a key regulator of NK cell function.

Purpose of the Study:

  • To investigate if NEO-201 can block the CEACAM5/CEACAM1 interaction.
  • To determine if blocking this interaction restores NK cell-mediated anti-tumor cytotoxicity.
  • To assess the efficacy of NEO-201 in enhancing NK cell activity against CEACAM5-expressing tumors.

Main Methods:

  • Utilized in vitro functional assays with human tumor cell lines and NK-92 cells.
  • Assessed NEO-201's ability to block CEACAM5 on tumor cells and CEACAM1 on NK cells.
  • Employed NK-92 cells as a model for direct NK cell killing, lacking antibody-dependent cellular cytotoxicity.

Main Results:

  • Expression profiling showed varied CEACAM5 and NEO-201 expression on carcinoma cell lines.
  • NEO-201 significantly enhanced NK-92 cell cytotoxicity against CEACAM5+/NEO-201+ tumor cells.
  • The enhanced cytotoxicity correlated with the level of CEACAM5+/NEO-201+ expression.

Conclusions:

  • NEO-201 effectively blocks the CEACAM5-CEACAM1 interaction.
  • NEO-201 reverses CEACAM1-dependent inhibition of NK cell cytotoxicity.
  • NEO-201 holds potential for enhancing anti-tumor immunity in CEACAM5-expressing cancers.

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