Cancers are notorious for hijacking the genome to support their growth and survival. One common trick used by tumors involves re-activating genes, such as NY-ESO-1, that are active during early development but are mostly silenced after we’re born.
In the case of ovarian cancer, tumors that produce NY-ESO-1 are more aggressive, but fortunately—according to a recently published study funded by the Cancer Research Institute (CRI) and conducted at Roswell Park Cancer Institute—this protein also makes these tumors more susceptible to immunotherapy.
Since 2002, a team led by Kunle Odunsi, M.D., Ph.D., Roswell Park’s deputy director and chair of the Department of Gynecologic Oncology, has evaluated more than 1,000 ovarian cancer patients. The doctors found that 40.7% of patients had tumors that expressed NY-ESO-1. These patients usually had more advanced disease, were less likely to respond to treatment, and experienced shorter survival times.
Therefore, Dr. Odunsi’s team developed a vaccine to target the NY-ESO-1 protein in these patients. In all, 68 ovarian cancer patients with NY-ESO-1+ tumors received vaccine. Study authors noted that these patients lived on average two years longer than patients who did not receive the vaccine, suggesting there may be an association between the vaccine and increased overall survival in this subset of NY-ESO-1+ ovarian cancer patients.
It should be noted that this study derived its findings retrospectively from the data of several different clinical trials and patient cohorts. Even so, Dr. Odunsi, a member of CRI’s Scientific Advisory Council, suggests in a Roswell Park press release announcing the study results that, “NY-ESO-1 be a high-priority target for future immunotherapy studies, given the high prevalence of NY-ESO-1 expression in ovarian cancer and the association of this tumor antigen with adverse clinical outcomes.”
Dr. Odunsi also believes that these findings “might be applicable to other cancers because NY-ESO-1 is the most immunogenic tumor antigen identified to date. Consequently, vaccination and/or cell-based immunotherapies targeting NY-ESO-1 are likely to be of significant benefit for all types of cancers.”
In addition to the above study, Dr. Odunsi currently co-leads a second CRI-funded Clinical Team, along with Hideho Okada, M.D., Ph.D., Lawrence Fong, M.D., and Pawel Kalinski, M.D., Ph.D., that’s exploring a combination immunotherapy approach against ovarian cancer.
Using a triple combination called CKM—which consists of IFN-α, TLR3 ligands, and celecoxib—they aim to enhance the ability of T cells to infiltrate and eliminate ovarian tumors, and ultimately improve survival in ovarian cancer patients. In addition to this strategy, which is currently being tested in both phase I and phase II clinical trials, Drs. Odunsi, Okada, Fong, and Kalinski are using preclinical cancer models to determine if checkpoint immunotherapy can increase the effectiveness of the CKM regimen.
Another CRI-funded investigator seeking to improve the therapeutic options for ovarian cancer patients is Juan Cubillos-Ruiz, Ph.D., a CLIP Investigator at Weill Cornell Medicine.
Dr. Cubillos-Ruiz’s work is investigating how certain lipid molecules can suppress immune responses against cancer and fuel tumor growth. Additionally, he’s determining how blocking the interactions between these lipids and immune cells, both alone and in combination with immunotherapies such as checkpoint inhibition and adoptive cell transfer, might contribute to more effective immunotherapeutic approaches that could improve survival for ovarian cancer patients.
In recognition of his contributions to ovarian cancer research, Dr. Cubillos-Ruiz was recently awarded the Pershing Square Sohn Prize for Young Investigators in Cancer Research.