Identification of a Native Novel Oncolytic Immunoglobulin on Exfoliated Colon Epithelial Cells: A Bispecific Heterodimeric Chimera of IgA/IgG*

Abstract

Understanding the nature of cell surface markers on exfoliated colonic cells is a crucial step in establishing criteria for a normally functioning mucosa. We have found that colonic cells isolated from stool samples (SCSR-010 Fecal Cell Isolation Kit, NonInvasive Technologies, Elkridge, MD), preserved at room temperature for up to one week, with viability of >85% and low levels of apoptosis (8% -10%) exhibit two distinct cell size subpopulations, in the 2.5 µM -5.0 µM and 5.0 µM -8.0 µM range. In addition to IgA, about 60% of the cells expressed a novel heterodimeric IgA/IgG immunoglobulin that conferred a broad-spectrum cell mediated cytotoxicity against tumor cells. In a cohort of 58 subjects the exclusive absence of this immunoglobulin in two African-Americans was suggestive of a germline deletion. Serial cultures in stem cell medium retained the expression of this heterodimer. Since a majority of the cystic cells expressed the stem cell markers Lgr5 and Musashi-1 we termed these cells as gastrointestinal progenitor stem cells (GIP-C**). CXCR-4, the cytokine co-receptor for HIV was markedly expressed. These cells also expressed CD20, IgA, IgG, CD45, and COX-2. We assume that they originated *This study was supported in part by NIH SBIR grants R44 DK56567 and R44 CA81799. **In this article, "SCSR cells" denote exfoliated cells isolated from stool samples and "GIP-C" are progenitor cells either present in SCSR cell isolates or cultured from SCSR cell isolates.

Germline Deletion of the Expression of a Human Bispecific Mucosal Immunoglobulin: Genetic Predisposition to Cancer and Communicable Diseases Predominantly among African-Americans

“…These concepts largely propagated through the utterances of sages from prehistorical times have not been corroborated by modern scientific methodology although they have received conceptual acceptance inferentially. This recent discovery of the existence of a genetic defect associated with the loss of expression of a protective broad spectrum bi-specific antibody (GIPSITUMAB ® , NonInvasive Technologies LLC, Elkridge, Maryland, USA) [8], among some ethnic communities (African-American, Asian) has opened the possibility of explaining how some individuals may not respond to prophylactic vaccines based on messenger RNA (blue print of viral protein).…”

“…During the course of our work with these exfoliated cells we noticed a significant number of cells expressed immunoglobulins [8]. This group of immunomimetic cells was thought to bear a significant influence on the nature of mucosal immunity.…”

“…About 70% of the cells were in the size range of 2.5 µ -5.0 µ, morphologically globular in appearance and the rest mostly 5.0 µ -8.0 µ, recognized by antibodies to antigens on goblet cells. A standardized procedure for detecting cell surface antigenic markers was developed and described in an earlier report [8].…”

“…

In a previous report we had reported on the discovery of a novel bispecific immunoglobulin expressed by colonic epithelial cells as they transform into immunomimetic cells during exfoliation (Albaugh et al (2020) Open Journal of Preventive Medicine, 10, 126-150). Colonic cells isolated from 0.5 gm aliquots of fresh stools (SCSR-10, Fecal Cell Isolation Kit, NonInvasive Technologies, Elkridge, MD) preserved at room temperature for up to one week, with viability of >85% were used to determine the number of cells expressing this novel bispecific immunoglobulin.

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Coprocytobiology: A Technical Review of Cytological Colorectal Cancer Screening in Fecal Samples

“…12,47 The field of coprocytobiology has advanced since it was first reviewed in 2003, producing novel methods and a series of contemporary publications. 4,7,13,16,18,43,47–56 The various cellular characteristics of colonic adenocarcinoma provide a rich landscape for the implementation of coprocytobiological techniques. Innovative isolation methods using existing and recent technologies could be further applied to improve the efficacy of fecal cytology and develop new screening regimes for colorectal cancer.…”