Identification Of A Native Novel Oncolytic Immunoglobulin On Exfoliated Colon Epithelial Cells: A Bispecific Heterodimeric Chimera Of IgA/IgG

Albaugh, G. P.; Dutta, S. K.; Iyengar, V.; Shami, S.; Lohani, A.; Sainz, E.; Kessie, G.; Nair, P.; Lagerholm, S.; Kamra, A.; Chen, J.-H. J.; Kalavapudi, S.; Shores, R. L.; Phillips, L.; Nair, R.; Nair, P. P.

doi:10.1101/140673

bioRxiv · 10.1101/140673

Identification Of A Native Novel Oncolytic Immunoglobulin On Exfoliated Colon Epithelial Cells: A Bispecific Heterodimeric Chimera Of IgA/IgG

Albaugh, G. P.·Dutta, S. K.·Iyengar, V.·Shami, S.·Lohani, A.·Sainz, E.·Kessie, G.·Nair, P.·Lagerholm, S.·Kamra, A.·Chen, J.-H. J.·Kalavapudi, S.·Shores, R. L.·Phillips, L.·Nair, R.·Nair, P. P.

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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 2.5M- 5.0 M and 5.0M-8.0M 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 from mature columnar epithelium by dedifferentiation. Our observations indicate that we have a robust noninvasive method to study mucosal pathophysiology and a direct method to create a database for applications in regenerative medicine.

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Albaugh, G. P., Dutta, S. K., Iyengar, V., Shami, S., Lohani, A., Sainz, E., Kessie, G., Nair, P., Lagerholm, S., Kamra, A., Chen, J.-H. J., Kalavapudi, S., Shores, R. L., Phillips, L., Nair, R., Nair, P. P.. 2017-05-22. Identification Of A Native Novel Oncolytic Immunoglobulin On Exfoliated Colon Epithelial Cells: A Bispecific Heterodimeric Chimera Of IgA/IgG. https://doi.org/10.1101/140673

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