Cancer Antibodies, Inc, together with Augusta University, the University of Virginia, and Tuning Fork Bio, presented a poster (#4109), at the recent AACR Annual Meeting, on identification of a cell-surface antigen on the surface of triple-negative breast cancer cells. In their poster abstract, the authors said the following. “Identification of druggable cancer-specific surface antigens is hindered by the complexity of cancer’s molecular diversity and the risk of normal cell cross-reactivity. We developed the Oncotope Platform that rapidly identifies multiple cancer-specific cell surface targets not expressed on normal cells (JCO 2022). In this study, we generated polyclonal antibodies to human triple-negative breast cancer (TNBC; Hs578T, ATCC). Following this, we used the Oncotope Platform to filter the anti-TNBC antibody-enriched serum, to yield cancer specific polyclonal antibodies. Using a protein microarray, we assessed the binding affinity of both the Total Anti-TNBC Serum (before filtration) and the Oncotope Filtered Anti-TNBC Serum towards approximately 25,000 human proteins. Our results identified antigens that exhibited significantly higher affinity binding to the Oncotope Filtered Anti-TNBC Serum than the Total Anti-TNBC Serum. One of these antigens, ZIP7, a zinc transporter situated in the ER and Golgi, has been shown to activate cell proliferation-related signaling pathways in TNBC. Our findings revealed the aberrant cell surface expression of ZIP7 on TNBC cells and its potential as a therapeutic target. Flow cytometry analysis using rabbit polyclonal antibodies against ZIP7 revealed substantial binding to TNBC cells, while no significant binding was observed with normal breast epithelial (NBE) cells from the same patient (Hs578BsT, ATCC). Additionally, cytotoxicity assays, employing the same antibodies and a secondary anti-rabbit ADC, showed the preferential killing of TNBC cells over NBE cells. In summary, our study marks a breakthrough in identifying cancer-specific antigens with therapeutic potential. The Oncotope Platform, in combination with protein microarrays, enables rapid identification of unique cancer-specific antigens absent in normal cells. Specifically targeting ZIP7 on TNBC cell surfaces highlights its promise for precision cancer therapy.”
In the conclusion of their poster, the authors said, “Our research marks a significant milestone as we are the first to reveal the cell surface expression of SLC39A7/ZIP7 in various types of breast cancer cells, distinctly absent in healthy breast epithelial cells and peripheral blood mononuclear cells (PBMC) from individuals without the disease. Importantly, our findings implicitly demonstrate the therapeutic targeting SLC39A7/ZIP7 on various breast cancer types using ADCs (Antibody Drug Conjugates), offering a precise and selective approach that avoids unintended interactions with adjacent healthy breast epithelial cells and other non-cancerous cell types. Furthermore, the identification of SLC39A7/ZIP7’s cell surface expression across diverse breast cancer cell types establishes it as a promising biomarker for breast cancer diagnosis.”