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Marc Theoret, MD, became intrigued with immunology early on his path to the medical profession, an interest that led him to the study of cancer biology. A combination of both of these fields has guided his research interests and also helped him develop the work that has earned him a 2008 ASCO Young Investigator Award (YIA). Dr. Theoret's YIA is sponsored by The ASCO Cancer Foundation Board of Directors and the ASCO Board of Directors.
"I was fascinated by the exquisite specificity of the adaptive immune system during college and medical school, and my experiences with patients who have been treated by conventional means for metastatic cancer clearly illustrated a need for more targeted approaches to cancer therapy," Dr. Theoret explained in an interview with ASCO Daily News. Today, his fascination with these topics continues as he develops research to investigate new immunotherapy treatments for patients with cancer.
Dr. Theoret is a graduate of the Pennsylvania State University (PSU) School of Medicine. After his third year of medical school, he participated in the Howard Hughes Medical Institute-National Institutes of Health (NIH) Research Scholars program for medical students, completing a 2-year fellowship. He earned his medical degree in 2001 from PSU and returned to the NIH for a post-doctoral research fellowship. Subsequently, he completed an internship and residency in internal medicine at Beth Israel Deaconess Medical Center. Currently, he is a Hematology and Oncology fellow at the National Cancer Institute (NCI), and he continues to study the intersections of immunology and cancer biology.
Specifically, Dr. Theoret investigates genetic therapeutic approaches that would give tumor reactivity to effector T cells that target the cancer antigens of common epithelial tumors in the NCI surgery branch. Although some studies have provided clues about T cell subsets that may be important for effective adoptive immunotherapy, Dr. Theoret explained that such studies are still in their infancy. He hopes to investigate this topic further and shed some light on this particular field of cancer research.
"Within the context of gene modified lymphocytes, I would like to initiate studies to more clearly define lymphocyte subpopulations that can mediate tumor regressions," he said.
Yesterday, Dr. Theoret presented research from his abstract, "In vitro and in vivo studies of human lymphocytes genetically engineered to express T cell receptors that recognize a p53 antigenic epitope" at the General Poster Session for Developmental Therapeutics: Immunotherapy. His work discussed the activity of these genetically modified lymphocytes against the pervasive tumor antigen commonly expressed on a wide variety of solid tumors.
"Isolating high affinity T cell receptors against self-antigens has been challenging in humans," he explained. "In this case, we utilized a T cell clone derived from a HLA-0201 transgenic mouse to isolate a T cell receptor capable of functioning in both CD8+ and CD4+ T cells."
After analyzing samples from patients who received such gene-modified cells, Dr. Theroet found that the transferred lymphocytes transduced with xenogeneic T cell receptors can persist. He hopes that his findings intrigued Meeting attendees and helped educate them about an exciting and developing field of cancer treatment.
"I hope that my presentation helped attendees gain insight into advances in adoptive immunotherapy with lymphocytes modified to express a self-specific T cell receptor capable of recognizing common cancers, specifically, some of the intricacies of redirecting the immune system against self-antigens such as p53," he said. "Although this area is still in its infancy, it appears to be a promising modality for the treatment of cancer."
Dr. Theoret received a 2008 YIA for his research proposal for a "Phase II study of metastatic cancer that overexpresses p53 using lymphodepleting conditioning followed by infusion of anti-p53 TCR-gene engineered lymphocytes." The award will provide him with the necessary funds to conduct research analyzing gene-engineered T cell survival and function in patients with metastatic cancers.
"The results of these immunologic studies will certainly direct my future adoptive immunotherapy efforts in patients with common cancers," he said. He also plans to continue his research by investigating anti-tumor T cell responses in patients receiving tumor-specific T cells and specific antigenic stimulation.
ASCO's YIA grants provide funding to promising investigators like Dr. Theroet in an effort to promote quality research in clinical oncology. These grants are awarded to fellows in their final year or first-year junior faculty members and are intended to fund physicians during their transition from fellowship to a faculty appointment. Dr. Theoret is grateful for the support ASCO has committed to his career goals and development.
"To successfully reach my goal as an independent laboratory and clinical investigator, grant support will be paramount in ensuring protected research time in my first academic position following my oncology fellowship," he said.
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