Abstract 4870: A novel potential target for cancer immunotherapy

Suppression of the host's immune system plays a major role in cancer progression. The tumor microenvironment (TME) not only plays a pivotal role during cancer progression and metastasis but also has profound effects on therapeutic efficacy. Immune checkpoint therapy, which targets regulatory pathways in T cells to enhance antitumor immune responses, has led to important clinical advances and provided a new weapon against cancer. This therapy has elicited durable clinical responses and, in a fraction of patients, long-term remissions. Several immune checkpoint inhibitors have been approved by the Food and Drug Administration (FDA), whose therapeutic effect is due to blocking the activity of proteins expressed in T lymphocytes (CTLA4, PD-1) and the interaction with surface protein expressed on tumor cells (PD-L1 and PD-L2). In our recent research activities we have identified 89 tumor-associated proteins by systematic immunohistochemistry analysis of tissue microarray (TMA) representing breast, colon, lung ovary and prostate cancer by using a large collection of polyclonal antibodies (approximately 1600) raised against membrane-associated and secreted proteins only marginally characterized. Among them, an interesting protein, which decorated the plasma membrane of breast cancer cells, was selected. This protein has been described to interact with the CD270/BTLA/CD160 pathway that regulates T-cell activation. It has also the capability to interfere with T-cell mediated allo-responses. Our characterization data showed that the protein is localized on the surface of several cancer cell lines. Moreover, it has the ability to stimulate cytokine production and secretion in PBMC from healthy donors. Several monoclonal antibodies have been generated in our lab against this protein and selected for the ability to bind the surface of cancer cells. Moreover, the ability of these monoclonal antibodies to interfere with the immune cells activity and to interfere with tumor growth in animal models is under evaluation. Results will be provided during the meeting. The currently approved therapeutic targets regimens for triple negative breast cancer and ovarian cancer have limited efficacy. Therefore, the identification of other tumor-associated proteins targetable by specific mAbs is essential to improve patient survival. Citation Format: Susanna Campagnoli, Matteo Parri, Alberto Grandi, Elisa De Camilli, Giuseppe Viale, Renata Maria Grifantini, Piero Pileri. A novel potent