The Program Project Grant will support dozens of investigators over the next five years as they accumulate data from a broad platform of bench science and translational research aimed at defining rational immunotherapy for the treatment of cancer.
"This is a tremendous achievement," says Dr. Clara Bloomfield, director of the OSUCCC. "The competition for Program Project Grants is intense; we feel the award is a clear reflection of the talent and energy in the OSU Cancer Center's Immunology Program."
"We are very excited about this award and what it means for the University, for science, and most of all, for the future of patient care. We have focused on bringing some of the best researchers in immunology to the University over the past several years, and that's a focus we will continue," says Dr. Fred Sanfilippo, senior vice president for health sciences at The Ohio State University and dean of the College of Medicine and Public Health.
Dr. Michael Caligiuri, associate director for clinical research at the OSUCCC and the principal investigator of the project, says there has been an explosion of new information in the past five years about how the innate immune system works, but those discoveries have yet to be translated into therapies that actually cure cancer patients, or even help them live longer. "The immune system is exquisitely complex, and may well hold the keys to the successful treatment of cancer, but we still have much to learn about its subtle machinery." Caligiuri says the award is the recognition of several years of sustained teamwork among many colleagues that have already led to new and critical understanding about how the innate immune system works.
The grant will support activities across four fully integrated projects, with many aspects of the research already under way. Specifically, the program projects include:
This is the "engine" that will drive the entire program - the clinical investigation of innate immunity among participants in several clinical trials involving leukemia or lymphoma patients at the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. Scientists hypothesize that some of the new, targeted therapies for cancer can be even more potent in the presence of agents called cytokines - hormone-like substances that may either inhibit or promote anticancer activities. Accordingly, all trial participants in the trials will receive a new biologic therapy, rituximab, plus the addition of either interleukin-2 or etanercept, agents that may affect rituximab's efficacy. Other new antibodies will also be tested in these diseases. The lead investigator of the project is Dr. John Byrd, an expert in blood malignancies and the D. Warren Brown Professor in Leukemia Research at Ohio State.
The clinical trial "engine" will be supported by three laboratory projects. The first, under the direction of Drs. Clark Anderson and Susheela Tridandapani, both members of the Department of Internal Medicine, will focus on integrating clinical findings with basic research in cell signaling. Scientists believe cell signals that regulate the functions of natural killer cells (NK cells) and other components of the immune system, called monocytes and macrophages, may activate or inactivate systems that directly impact the effects of antibody therapies against cancer.
Caligiuri will lead another laboratory project exploring the role of two key subsets of NK cells that appear to be important players in the immune response. Through earlier studies, Caligiuri and his colleagues determined that the two subsets (dubbed CD56 bright and CD56 dim in humans) are functionally distinct, much the way the body's T cells are. A major goal of this project is to further understand the genes that make these subsets different, and modulate them for better cancer therapy in combination with antibodies.
Fundamentally integrated with all of the projects is the development of appropriate mouse models that offer researchers insight into how various strategies modulating the immune system may actually work in humans. Dr. Yang Liu, a professor of pathology, who will direct this part of the program, recently found subsets of mice NK cells that are strikingly similar to the CD56 bright and CD56 dim subsets found in humans. In addition, Liu will also study how the co-stimulatory molecules B7 and B1 may enhance the anticancer activities of NK cells.
The infrastructure to support the work over the past two years, culminating in the $9.5 million award, came from a new program at the Comprehensive Cancer Center that brings scientists with cancer expertise together to form teams in tackling a cancer problem. The rich mix of basic science and clinical exploration will be supported by a myriad of core Cancer Center facilities at Ohio State, including biostatistical support led by Dr. Stanley Lemeshow, clinical correlates directed by Dr. William E. Carson, animal facilities led by Dr. Liu, and administrative support from the Clinical Trials Office at The Comprehensive Cancer Center and The James.
"We believe we have a strong, cohesive and highly-motivated group of researchers who will be able to very quickly translate basic science into better patient care," says Caligiuri. "That's what it's all about. We couldn't be more excited."