The overall goal of the University of Texas MD Anderson Cancer Center Ovarian SPORE is to prolong survival and to reduce the number of deaths from ovarian cancer through innovative research in the detection and treatment of ovarian cancer. The investigators funded by this grant have worked together to conduct five separate research projects. Project 1 has evaluated new biomarkers to create a blood test for early detection of ovarian cancer. When ovarian cancer is detected in stage I, up to 90% of women can be cured; however, only 20-25% of women are currently diagnosed at this stage. Detection of early stage disease in a larger number of women could improve the cure rate by 15–30%. Project 2 has tested drugs that can overcome the resistance that is developed to current therapy which targets the blood vessels that grow into and bring nutrients to ovarian cancer cells. Increasing the ability of drugs to eradicate the tumor blood supply will help kill the cancer cells. Project 3 has tested drugs for personalized therapy for low- grade cancer. Low-grade ovarian serous carcinoma is more common in younger women and it is a unique disease that is highly resistant to standard chemotherapy and difficult to manage. The goal of this project is to improve understanding of how low-grade ovarian cancer develops and progresses in order to identify new drug therapies that limit its growth. Project 4 has studied drugs for personalization of treatment for high grade ovarian cancers. Not all ovarian cancers will respond the same way or to the same extent to the chemotherapy drugs currently available or to the targeted therapies that are becoming the standard of care. This is due to molecular variation that exists from person to person and from cancer cell to cancer cell in the same patient. Finally, Project 5 has created modified cells that can be used to deliver a therapeutic agent directly to the ovarian tumors. Bone marrow-derived mesenchymal stem cells (MSC) are collected from an individual and modified in a test tube using recombinant DNA techniques. The modified cells are then injected into the patient and will move through the blood stream and ultimately integrate into the ovarian tumors. Once engrafted in the tumor, the modified MSC will produce a potent anti-tumor molecule which acts to reduce cancer cell growth.
Current therapies fail to cure 40% of breast cancer patients, who relapse and die from drug-resistant disease. Immune-based therapies work differently than drugs that destroy tumor cells directly by recruiting the patient’s own immune system to seek out and kill tumor cells. Immune-based therapies are not limited by drug resistance, are highly specific, and typically have few side effects. Importantly, they uniquely result in a durable therapeutic impact due to memory. Immune-based therapy includes vaccines and antibodies. Vaccines activate long-lasting T cells that kill existing cancers, and can remember to kill tumors should they arise again. Antibodies target proteins such as HER-2 on cancer cells, and immune cells bind these antibodies to kill tumors. HerceptinR is a HER-2-specific antibody that significantly improves the survival of patients with early and metastatic HER-2hi breast cancer.
Because tumors arise from the patient’s own tissues, the immune system sees them as “self” rather than as dangerous invaders (like an infection). A special type of regulatory T cell (Treg) keeps the immune system from recognizing “self”, and prevents tumor immunity. Low doses of the chemotherapy drug cyclophosphamide (CY) can reduce Tregs in breast cancer patients, sparing the good T cells needed to fight cancer. HER-2-specific antibodies can supercharge our cell-based vaccine by forming a bridge between HER-2 on the vaccine cells and host dendritic cells. Antibody-supercharged dendritic cells generate more killer/memory T cells of higher quality than dendritic cells alone. Our ongoing analysis of T cells from patients treated with CY, Herceptin and vaccine suggests that the T cells are of higher quality. We continue to test this strategy in patients with HER-2lo metastatic breast cancer, where Herceptin does not fight breast cancer directly. We have enrolled about 65% of the planned 60 patients. Our integrated clinical studies will identify the most active combination vaccine regimen to test for preventing relapse patients with early breast cancer, regardless of HER-2 expression level.
