Vaccines to Prevent Ovarian Cancer Recurrence
The biggest challenge in ovarian cancer isn’t getting to remission - it’s staying there. Recurrence rates are high, especially for advanced disease. Nineteen-year survivor and CVI vaccine recipient Jamie Crase captures that stark reality: “Stage 4 ovarian cancer has a 90-95% chance of recurrence after the initial treatment. The odds were not in my favor.”
At the Cancer Vaccine Institute, we are changing the odds in the favor of Jamie and all patients diagnosed with this deadly disease. We are developing vaccines that specifically program the immune system to seek and destroy any ovarian cancer cells that might be lingering after initial treatment - and prevent them from giving rise to a recurrence. The vaccines are designed to target proteins that are abnormally expressed in ovarian cancer and play a key role in driving tumor growth. We currently have three vaccines that are designed to prevent ovarian cancer recurrence: IGFBP-2, OVAC, and STEMVAC.
IGFBP-2 vaccine advances to phase II clinical trials
The IGFBP-2 vaccine programs the patient’s immune system to recognize a protein found at high levels in ovarian cancer cells. We saw remarkable results when we tested the IGFBP-2 vaccine in a Phase I clinical trial in patients with advanced-stage or recurrent ovarian cancer who had been treated to complete remission. We vaccinated patients, and then followed them for 8 years. The vaccine was safe; 98% of the side effects were minor, like those seen with the flu or covid vaccines. Importantly, the vaccine was effective: more than half the patients were alive 8 years after getting the vaccine and one third had not had their cancer come back. Without the vaccine, we would expect only half of the patients with advanced stage ovarian cancer to live past a year and a half.
Based on these exciting results, Dr. John Liao has recently opened a Phase II clinical trial for the IGFBP-2 vaccine at the CVI that is now recruiting patients. The Phase II study, generously funded by the Kuni Foundation, is evaluating the vaccine in patients who are showing the earliest signs of recurrence – rising levels of the CA125 tumor marker without any evidence of cancer on scans. We know that recurrence is imminent in these patients but currently there is no effective treatment to prevent the recurrence from occurring. By vaccinating patients with increasing CA125 levels, we hope to create cancer-killing immune cells that can find and destroy the few cancer cells that are the beginnings of a recurrence and stop it in its tracks. You can find more information on this open clinical trial here.
OVAC: A multi-targeted approach
Cancer growth and metastasis can be driven by many different changes in cancer cells. We’ve learned over the course of our cancer vaccine research that we get better protection against cancer by targeting multiple cancer proteins to prevent cancer cells from escaping the immune system. As a result of these findings, we are developing a next generation ovarian cancer vaccine called, OVAC, that targets IGFBP-2 and three other ovarian cancer proteins. OVAC is currently in preclinical testing where we’ve shown that it creates strong anti-cancer immune responses and effectively reduces ovarian tumors in mice. When we give the mice vaccines with current standard of care therapies, we see much more effective tumor reduction than the standard therapies alone. We believe OVAC will not only improve response of standard therapies but provide long-term immune protection against future recurrence. Over the next 12 to 24 months, we will complete the final studies in mice to confirm vaccine effectiveness and safety, in order to apply to the FDA for approval to evaluate the vaccine in a human clinical trial.
STEMVAC: Targeting cancer-driving stem cells
STEMVAC is a vaccine that targets a small subset of tumor cells that are known as cancer stem cells that can drive growth, drug resistance, and metastasis in many kinds of cancers, including ovarian cancer. We have evaluated STEMVAC in breast cancer and found that the vaccine creates strong anti-cancer immune responses. We believe that STEMVAC will be an effective tool for the treatment and recurrence prevention in ovarian cancer as well. Moreover, STEMVAC may be an effective tool for preventing cancer from occurring in the first place in patients who might be at genetic high risk - a topic we will explore later this month.
The CVI is tackling the biggest problem faced by ovarian cancer patients - recurrence. We think that generating effective, long-term immune protection is going to change the odds for a disease that has created suffering for many. We have advanced an effective ovarian cancer vaccine (IGFBP-2) in clinical trials and we have a multi-antigen vaccine moving rapidly through our preclinical pipeline - we hope to have this in clinical trials for treatment and prevention of recurrence in the next 24 - 36 months. With STEMVAC, we have another option in our ovarian cancer arsenal that may be effective at not only treatment but prevention.
