Colonic Epithelial Cells Express an Oncolytic Bispecific IgA/IgG heterodimer

Abstract

The gastrointestinal epithelium sheds about 10(12) cells per day. Contrary to conventional wisdom a majority of these cells (>90%) are excreted into the fecal stream intact. We first demonstrated the isolation of these cells in a viable state (1991) and showed the feasibility of studying the expression of various bomarkers in health and disease. During the course of our studies mapping the expression of surface markers using flow cytometry we discovered that these cells had the ability to destroy a variety of cancer cells. These colonic cells expressed among other markers (COX‐2 during an inflammatory condition) IgA and IgG along with a subpopulation of cells co‐expressing IgA/IgG. Blocking the IgG component with anti‐IgG antibody discharged the oncolytic property of these cells. We also observed that these cells expressed Lgr5 and Musashi1, the putative markers of gastrointestinal progenitor stem cells. Long term tissue culture experiments revealed the persistence of the heterodimer. In a cohort of 80 random human samples we observed the absence of this hybrid IgA/IgG antibody in two subjects of African American origin. Lineage directed differentiation of these cells generated a progeny that secreted this chimeric antibody. This antibody was shown to arrest the growth of human colon cancer in xenotransplants in nude mice. From these observations It was concluded that this is a novel native antibody that may be absent in certain individuals as a result of a genetic aberration.Support or Funding InformationSBIR grants R43 & R44 DK‐56567 and R‐43 & R‐44 CA‐81799 from the NIDDK and NCI of the National Institutes of Health.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.