Researchers in the Department of Immuno-Oncology are pioneering medical science that harnesses the power of the body’s own immune system to fight cancer. Immunotherapy is a formidable weapon against cancer because of its potential to exploit the body's natural defenses against infection.
Two cancer immunotherapies currently in use are T cell therapy, which uses specialized cells produced by the immune system to target and kill cancer cells, and immune checkpoint blockade, which modulates/enhances the immune system to attack and kill tumor cells. These therapies are effective for some patients with metastatic cancer. They also offer renewed hope to people who have exhausted other treatment options.
But scientists in the Department of Immuno-Oncology foresee a much larger role for immunotherapy in the battle against cancer. They intend to move immunotherapy forward to the front lines by making it a highly effective primary treatment option, capable of producing more powerful, less toxic cures. Our scientists are working to further enhance the efficacy of these novel treatments, and to apply them to patients with early-stage cancer to eliminate microscopic residual disease which can lead to cancer recurrence, even after chemotherapy, radiation therapy and surgery have been successful.
Peter P. Lee, M.D., Chair
Dr. Lee seeks to utilize immunotherapy as a less toxic approach to treating patients diagnosed with breast and other cancers. While many researchers focus on attacking the cancer cell itself, Dr. Lee aims to target the cancer cell as well as its ‘co-conspirators’ — support cells within the tissue stroma and tumor microenvironment. In order to survive, cancer cells recruit and manipulate these support cells, and as a result, a patient’s immune system is destroyed. Right now, Dr. Lee is studying these co-conspirator cells to broaden his understanding of their interactions. By gaining a better understanding of the ways these co-conspirators help feed cancer cells, he may be able to develop therapeutics that target both malignant cells and their supporting cells — thereby, restoring and enhancing the immune function in patients with breast cancer.
An international expert in leukemia, lymphoma and bone marrow transplantation, Dr. Forman helped build City of Hope’s Hematologic Malignancies Program into one of the largest and most successful programs in the world. Dr. Forman's work also focuses on immune-based therapies for treating malignancies, specifically the potential of augmenting the antitumor response of T cells, the body's immune defense against infection and cancerous cells.
Dr. Brown is The Heritage Provider Network Professor in Immunotherapy and a professor in the departments of Hematology & Hematopoietic Cell Transplantation and Immuno-Oncology. Dr. Brown conceptualizes, performs and oversees studies to evaluate CAR design, T cell manufacturing, cell-based immunological assays and in vivo animal models. As deputy director of the T cell Therapeutics Research Laboratory (TCTRL), she also leads multifunctional teams to translate these therapies to the clinic, participating in all stages of the regulatory process. Dr. Brown provides scientific oversight for TCTRL adoptive T cell therapy clinical activities and serves as co-principal investigator on 10 investigational new drugs using adoptive T cell therapy. Dr. Brown also leads research efforts aimed at developing and optimizing chimeric antigen receptor (CAR) T cell therapies for the treatment of cancer. Dr. Brown’s research program is primarily focused on developing CAR T cells for the treatment of brain tumors, both primary and metastatic. Over the past two decades, Dr. Brown has contributed significantly to the advancement of CAR T cell therapy by development and optimization of novel glioblastoma-targeted CAR T cells, improvements in T cell manufacturing and optimization for routes of T cell administration for brain tumors. Dr. Brown’s research efforts have been instrumental in initiating five first-in-human clinical trials for treatment of glioblastoma, including ongoing clinical testing of IL13Rα2-, HER2- and CLTX-directed CAR T cell therapies (NCT02208362, NCT03389230, NCT04214392, and NCT03696030). To translate these CAR therapies to the clinic, Dr. Brown leads multifunctional teams and has a strong track record in mentoring scientists at all stages of their career.
Dr. Kortylewski focuses on the development of novel cancer immunotherapies based on targeting transcription factors, such as STAT3, which are convergence points for tumorigenic signaling from multiple surface receptors and kinases. His novel two-step immunotherapeutic strategy is first to disarm tumor defense systems by targeting immune checkpoint regulator, STAT3, and then to unleash potent antitumor immune responses by stimulation of toll-like receptor-9 signaling. Oligonucleotide therapeutics based on this strategy are currently in preclinical testing before clinical application for treatment of leukemia, lymphoma and certain solid tumors, such as prostate cancers.
Dr. Kortylewski received his Ph.D. in molecular biology from the University School of Medical Sciences in Poznan (Poland). He then completed two postdoctoral fellowships: in cancer biology at the Institute of Biochemistry (Aachen, Germany) and in tumor immunology at H. Lee Moffitt Cancer Center (Tampa, Florida). As an independent investigator, his team develops oligonucleotide-based STAT3 inhibitors for immunotherapy of human cancers. The first generation siRNA-based molecule currently undergoes safety and tolerability studies assisting IND filing. Research from Dr. Kortylewski’s laboratory has earned notable funding from major federal and private sources, including the National Institutes of Health/National Cancer Institute, the Department of Defense — Prostate Cancer Program, ThinkCure, Margaret E. Early Medical Research Trust, STOP CANCER and the Prostate Cancer Foundation.
Dr. Yu’s laboratory was the first to validate STAT3, a critical regulator of tumor cell survival and proliferation, as a molecular target for cancer therapy in animal models. Yu's team also discovered the critical role of STAT3 in tumor angiogenesis and tumor immune evasion.
She and her colleagues have devised a novel biologic-based drug called CpG-Stat3 siRNA that strikes a dual blow against cancer. It blocks the growth of tumor cells directly, and activates surrounding immune cells to attack the tumor. This drug takes advantage of two components, which block production of the cancer-promoting and immunosuppressive protein STAT3, and direct the therapy specifically to immune and tumor cells. Importantly, CpG-STAT3 siRNA overcomes the limitations of small molecule drugs, which are difficult to design against proteins such as STAT3 that have no enzymatic activity. It also serves as a unique therapeutic platform, as the siRNA can be designed to block virtually any protein of interest that is important for cancer growth and proliferation. In pre-clinical studies, CpG-STAT3 siRNA effectively stymies growth of aggressive lymphomas and the brain cancer glioma, two deadly cancers with no current viable therapies. A clinical grade CpG-STAT3 siRNA is scheduled to begin production at City of Hope’s facilities this year, and Dr. Yu and her colleagues are poised to take this leading-edge therapeutic strategy to first-in-human clinical trials within two years.
Identifying the Connection between Stat3 and Diabetes — It has long been established that obesity is a major cause of type 2 diabetes, due in part to specific cells in fat tissue that promote pathogenic T cells and blunt the activity of insulin. Dr. Yu is exploring the connection between STAT3 and the development of diabetes. In efforts to learn more about this potential link, her lab has used genetically-engineered mice whose T cells lack the STAT3 gene. When these mice became obese through forced consumption of a fatty diet, they showed better glucose tolerance compared with comparably overfed normal mice, as well as a shift in the balance of pathogenic T cells toward regulatory T cells. These intriguing findings suggest that STAT3 is common to both cancer and diabetes and suggest that anti-STAT3 therapies, which have thus far been considered primarily for cancer, might also be effective against type 2 and perhaps type 1 diabetes.