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Federal stimulus package funds innovative cancer studies

Robert S. Negrin, MD

By Elizabeth Crown

Three Stanford Cancer Center researchers have received highly coveted, multimillion-dollar “Grand Opportunities (GO)” grants from the National Institutes of Health. The GO grant program is one of a number of NIH initiatives funded as part of the $787 billion federal stimulus package, also known as the American Recovery & Reinvestment Act of 2009.

The GO grant program supports projects that address large biomedical and other research projects that will benefit from significant two-year funding. Projects are funded based on their potential to provide a high short-term return and display an increased likelihood of enabling growth and investment in biomedical research and development, public health and health care delivery.

One of the Stanford Cancer Center’s GO grant-funded projects is headed by Robert S. Negrin, MD, professor of medicine, chief of the division of Blood and Marrow Transplantation and medical director of the Clinical Bone Marrow Transplantation Laboratory. His project, “Regulatory T Cells in Allogeneic Transplantation,” was awarded nearly $2 million over two years. The grant will allow Negrin and his research colleagues to translate several major projects using cellular therapeutics to treat patients with cancer. The award will support required equipment and provide critical new personnel in the form of a translational team to bring these projects from the laboratory to the clinic.

The lead study in this project will apply regulatory T cells to allogeneic hematopoietic cell transplantation to reduce the risk of graft versus host disease and improve immune reconstitution. Additional plans include the development of purified hematopoietic stem cells for transplantation without graft versus host disease, common lymphoid progenitors to improve immune reconstitution and memory CD8+ T cells to treat or prevent disease relapse.

Negrin’s collaborators on this project are Samuel Strober, MD; Judy Shizuru, MD; Kenneth Weinberg, MD; Kevin Sheehan, MD; Philip Lavori, PhD; Ginna Laport, MD; and Robert Lowsky, MD.

The second project to receive a GO grant is led by Albert J. Wong, MD, professor of neurosurgery and director of the Brain Tumor Research Laboratories, and Paul G. Fisher, MD, professor of neurology & neurological sciences, pediatrics and (by courtesy) neurosurgery. The two-year, $1.5 million award will fund a phase I clinical trial investigating the use of the anti-EGFRvIII vaccine for pontine gliomas in children.

Diffuse intrinsic pontine gliomas are the most deadly and intractable of the pediatric brain tumors, with a median overall survival of nine to 10 months. Over the last 20 years, there have been numerous clinical trials using different combinations and timing of radiation and chemotherapies that failed to prolong survival.

Part of the difficulty with treating this tumor is a lack of understanding of its basic biology due to a short supply of tumor samples. Because surgery is not part of the treatment for pontine gliomas, there is no source of tissue to study. Thus, improved in vitro methods of studying these tumors are needed.

The EGFRvIII vaccine is one of the most promising agents for the treatment of glioblastoma, the most common malignant brain tumor in adults. Initial phase II studies with the vaccine demonstrated more than a doubling of overall survival when compared with historical controls.

Recent studies have demonstrated EGFRvIII expression in about 50 percent of pediatric diffuse intrinsic pontine gliomas. Thus, EGFRvIII warrants investigation as a target for these deadly pediatric tumors, the researchers said.

Wong and Fisher’s project will assess the safety and tolerability profile of EGFRvIII peptide vaccination in pediatric patients, determine overall survival of patients treated with the vaccine after conventional radiation and evaluate humoral and cellular immune responses to explore overall immunogenicity of the vaccine.

Additionally, the researchers will study tumor microvesicle secretion into the cerebrospinal fluid of children with diffuse intrinsic pontine gliomas to examine the protein expression and/or alterations in certain genes from these samples that can be used as a diagnostic tool and improve understanding of this tumor’s biology.

Posted 10/13/09

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