Targeting Ovarian and GI Cancers: The Development and Efficacy of NEO-201 Monoclonal Antibody

A new humanized IgG1 monoclonal antibody, NEO-201, has been developed that homes in on a specific neoantigen found on ovarian and gastrointestinal (GI) cancers. Unlike CEACAM, this antigen is unique to tumor tissues, making it a promising target for cancer therapy. The study had two primary goals: to assess the presence of this antigen in various tumor cell lines from ovarian and GI cancers, and to examine the effectiveness of NEO-201.

The antigen's presence was confirmed through western blot analysis and flow cytometry. The functionality of NEO-201 was evaluated using an antibody-dependent cell-mediated cytotoxicity (ADCC) assay with cell lines that tested positive for the antigen. Non-expressing cell lines served as negative controls. The ADCC assay utilized natural killer (NK) cells derived from peripheral blood mononuclear cells (PBMCs) of healthy donors, as well as high-affinity activated NK (haNK) cells. HaNK cells, which are NK-92 cells modified to express a high-affinity human CD16 variant and the human IL-2 gene, lack inhibitory killer cell immunoglobulin-like receptors, potentially enhancing their cytotoxic capabilities.

Results from the western blot analysis identified the NEO-201 antigen in two ovarian cancer cell lines (OV90 and PE01) and one colorectal cancer cell line (LS174T). Flow cytometry further confirmed the antigen's expression in additional cancer cell lines, including one ovarian (OV90), one colorectal (LS174T), and two pancreatic cancer cell lines (ASPC-1 and CFPAC-1). The ADCC assay showed that NEO-201 could induce tumor cell death on its own; however, the presence of NK cells or haNK cells significantly increased the lysis of tumor cells expressing the NEO-201 antigen.

The study concludes that the NEO-201 antigen is expressed in several tumor cell lines from ovarian and GI cancers, and that NEO-201 can effectively mediate ADCC activity with NK cells and NK cell lines. Moreover, NEO-201 can trigger apoptosis in tumor cell lines that express the antigen. Preliminary data also indicates the antigen's presence in a variety of cancer types. The team plans to conduct in vivo studies and investigations related to the Investigational New Drug (IND) application process.

The research was presented by Kristen Zeligs and colleagues at the American Association for Cancer Research Annual Meeting in 2017.