University of Pittsburgh researchers have isolated four novel human antibody secreting plasma cell lines from ovarian tumor tissue and ascites. The cells have undergone spontaneous immortalization in vitro and are continuously secreting monoclonal antibodies. These patient-derived novel cell lines have the potential to identify therapeutic targets in ovarian cancer.
Description
Epithelial ovarian cancer (EOC) has a 5-year survival rate of less than 50%, partially due to late diagnosis after tumors have spread beyond the ovaries to the peritoneal cavity. Using tissue from different high-grade serous epithelial ovarian cancer (EOC) patients, four unique antibody secreting plasma cell lines were isolated. The antigens recognized by three of the four cell lines are coil-coil domain containing protein 155 (CCDC155), growth factor receptor-bound protein 2 (GRB2), and pyruvate dehydrogenase phosphatase2 (PDP2), respectively.
Applications
• Personalized oncology
• Biomarker development
• Source of tumor antigen binding, human monoclonal antibodies
Advantages
These newly isolated plasma cell lines are immortalized in an antibody-secreting state, and can be continuously propagated, allowing for widespread use in research. Immortalization occurred spontaneously during in vitro cell culture and was due to the presence of Epstein Barr Virus (EBV), most likely linked to patients’ exposure to EBV infection earlier in life. These lines have been derived from ovarian tumors with tertiary lymphoid structures (TLS)-like structures comprising of T and B cells and their formation in solid tumors is linked to a positive outcome. TLS is only seen in a small number of EOC patients and the availability of cell lines from patients with these characteristics could enhance research into the role of TLS in EOC. EBV genes can act as oncogenes and may contribute to proliferation of B cells in solid tumors. These cell lines allow for further basic studies on immunoglobulin secretion by tumor isolated B cells, represent novel tools for studies on the role of B/plasma cells and consequence of EBV in EOC, which could potentially be harnessed for immunotherapy. Additionally, the human antibodies secreted by these cell lines could be used for new antigen discovery and/or biomarker assay development, to add earlier diagnosis of EOC and improving patient outcomes.
Invention Readiness
From clinical samples (tumor tissue and ascites) of patients with high grade serous EOC, cell lines BOC-36, BOC-73, BOC-78 and BOC-89 were isolated and immortalized ex vivo. All four cell lines were found to secrete antibodies. Cell line BOC-36 is monoclonal and secretes IgG1,k antibodies, BOC-73 is oligoclonal and secretes IgG1,k and l antibodies, BOC-78 secretes monoclonal IgM,k antibodies and BOC-89 secretes a mixture of IgG1,k and IgG3,k. All antibodies were tested against a library of 20,000 different proteins revealing several potential candidate antigen targets. The antibodies secreted by cell lines BOC-36, -73 and - 89 recognize CCDC155, PDP2 and GRB2.
IP Status
Pending
