Enhancing Immunotherapy with Novel Combinations to Improve the Treatment of Primary and Metastatic Colon Cancer
Abstract
Colorectal cancer is the most common cancer of the digestive tract and is one of the deadliest cancers worldwide, primarily by spreading to the liver. It is extremely common in U.S. Department of Veterans Affairs (VA) patients, and it is becoming increasingly found in younger Service men and women, as opposed to in the general population, where it is mostly seen in retirees. Furthermore, scientists have proposed that Service members may be at increased risk for this cancer due to specific military exposures and infections while deployed overseas. Thus, research that addresses new and more effective treatments for this deadly disease addresses a FY18 Military Relevant Focus Area, and is important for not only the general public, but is critical for the future well-being of military members, Veterans, and their beneficiaries. Treatment of advanced colon cancer has not changed significantly in decades, and new approaches are clearly needed to improve outcomes. One of the most exciting cancer therapies that has been effective in other cancers is immunotherapy. This approach utilizes the patient’s own immune system to recognize cancer cells as a foreign invader, and it clears the body of tumors often without chemotherapy or radiation. This approach has been unsuccessful in more than 95% of colon cancers, and we hypothesize that this is due to inhibitory signals in the tumor that block our body’s specialized cancer-fighting immune cells. Our lab has formulated a strategy to increase the number and strength of cancer-fighting immune cells that invade colon tumors and liver metastases. When we combine this strategy with a medicine that blocks the inhibitory signals made by the tumor, the cancer is dealt a swift one-two punch that appears to effectively kill the cancer cells in both locations. We propose to study this combination, understand how it works, develop ways to make it more effective, and to test it on human colon cancers that we removed from patients in the operating room. Thus, our research addresses FY18 PRCRP Topic Areas of (1) colorectal cancer, (2) liver cancer, and (3) immunotherapy. Our preliminary data is already very exciting in mouse models of colon cancer and liver metastases that reflect the human course, and at the conclusion of this study we expect to deliver combination immunotherapy in a clinically relevant fashion to impart anti-tumor immune responses in human tumors. At that time, these findings will be directly translatable into clinical trials for patients with advanced colon cancer. Since the current use of anti-CTLA4 immunotherapy imparts a response in only a minority of people and only in a few immunogenic tumors, a better understanding of its efficacy in combination with our intervention, LIGHT, could not only enhance its response rate, but also vastly increase its indications in previously unresponsive tumors in addition to colon cancer. Thus, the implications of our proposed study have the near-term potential to improve patient quality of life and survival over the best current surgical and chemotherapeutic strategies available for this disease and many other “cold” digestive disease cancers.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910457
Entities
People
- Ajay Maker
Organizations
- United States Army
- University of Illinois at Chicago