The University of Texas MD Anderson Cancer Center and GlaxoSmithKline (GSK) have signed a research collaboration and license agreement to develop new therapeutic antibodies that promote an immune system attack against cancer.
Under terms of the agreement, MD Anderson grants GSK exclusive worldwide rights to develop and commercialize the antibodies, which activate OX40 on the surface of T cells. They were discovered by Yong-Jun Liu, M.D., Ph.D., and colleagues when he was professor and chair of MD Anderson's Department of Immunology.
MD Anderson, through its new Institute for Applied Cancer Science (IACS), will collaborate with GSK to conduct preclinical research on the antibodies.
"This agreement is not only a tribute to the ability of MD Anderson scientists to discover new targets and potential therapies against those targets for cancer patients, it's also a testament to the vision shared by GSK and MD Anderson that successful clinical development of oncology drugs requires seamless integration of drug development expertise and deep biological knowledge," said Giulio Draetta, M.D., Ph.D., IACS director. "The IACS was formed to enable precisely such integration to expedite the accurate translation of great science into drugs."
The overall potential value of the agreement to MD Anderson over the life of the agreement is estimated at more than $335 million. Under the terms of the agreement, MD Anderson will receive an upfront license payment and funding for IACS research collaboration activities, as well as payments for reaching development, regulatory and commercial milestones. In addition, MD Anderson will also be entitled to royalties deriving from the commercial sales of products developed under the collaboration.
"We're excited about this opportunity with GSK to improve cancer treatment," Draetta said. "The IACS is a drug development engine with industry-seasoned scientists embedded in a comprehensive cancer center, and as such is ideally suited for this type of collaboration."
The institute is a vital platform resource for MD Anderson's recently announced and unprecedented Moon Shots Program, which focuses resources and diverse expertise to significantly reduce mortality in the short term and promote cures long term, beginning with eight inaugural cancers.
Unleashing the immune system
Malignant cells are an abnormality that usually attracts a response from the body's immune system, yet cancer often survives by evading or thwarting anti-tumor immunity. Consistently unleashing the power of the immune system against cancer would be a major step forward for cancer patients.
T cells are lymphocytes, a type of white blood cell produced by the thymus, equipped with receptors that recognize and bind to antigens, which may include abnormal cells.
"T cell recognition of a tumor antigen is not enough to activate the T cells against cancer cells, they need a secondary signal to tell them 'that antigen you have is a bad thing, you have to attack,'" said Liu, who is now chief scientific officer and vice president of the Baylor Research Institute of the Baylor Health Care System in Dallas.
OX40 is one of these secondary or co-stimulatory receptor proteins. Liu and colleagues found that when it's activated, it enhances immune attack and blocks suppressors of immune response.
Liu and his MD Anderson colleagues generated and screened hundreds of antibodies that could potentially act as on switches for OX40 by mimicking its natural activator, OX40L, a molecule that binds to OX40. Years of research narrowed the candidates to a handful of activators, or agonists, which were tested in mice and then altered for human use.
"It's gratifying to see MD Anderson and GSK take this important step towards translating a basic science discovery into a potential new therapy that can proceed to clinical trial," Liu said.
Initial clinical trials will occur only after necessary preclinical drug development conducted under the agreement succeeds.