by Kathleen O’Neil

Stephen Forman  (Photo by Marcelo Coehlo)

The W.M. Keck Foundation has awarded investigators at City of Hope and the California Institute of Technology a $450,000 grant to study the molecular mechanisms underlying lymphoma and develop new treatments for this disease. The pilot grant includes the chance to renew funding for as much as $1.55 million through 2010.

Lymphoma is a group of cancers of the immune system. It represents the fifth most common form of cancer in the United States, is increasing in incidence and can affect people of all ages. Current treatment options — chemotherapy and radiation — are not curative for many types of lymphoma, and many patients experience relapse. The grant will support City of Hope and Caltech scientists who are developing new therapies that would destroy lymphoma cells without harming healthy cells, reducing side effects.

“This unique research team, made up of senior investigators at City of Hope and Caltech, is particularly qualified to expand our understanding of these cancers,” said Michael A. Friedman, M.D., president and chief executive officer of City of Hope. “This grant from the W. M. Keck Foundation will help us develop better treatments for lymphoma that may also apply to other types of cancer.”

Researchers will use nanotechnology to try to focus cancer-fighting drugs where they are safest and most effective.

The scientists will employ cyclodextrin-containing polymers — molecules that do not stimulate the immune system and have very low toxicity — originally designed by Mark Davis, Ph.D., Warren and Katharine Schlinger Professor of Chemical Engineering at Caltech, and his colleagues. The team will direct the polymers to cells using engineered lymphoma antibodies (developed at City of Hope) so they will target only cancerous cells. Once inside the cells, the polymers will deliver their payload: pieces of genetic material called short interfering RNA, or siRNA, that disrupt the genetic coding in cancer cells to either kill the cells or render them unable to multiply. Researchers will target several known genes in the tumors’ DNA and plan to identify new genetic targets, as well.

“These studies will expand our understanding of how lymphoma develops, and will also establish a proof-of-principle for this type of targeted, molecular-based therapy in the treatment of lymphoma,” said Stephen Forman, M.D., the Francis and Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation at City of Hope and principal investigator of the study. “Patients would greatly benefit from less-toxic therapies for lymphoma, particularly older patients, who are most often affected and may not be able to tolerate intensive treatments.”

Mark Davis   (Courtesy of Caltech)

Caltech investigators include Davis and Scott Fraser, Ph.D., the Anna L. Rosen Professor of Biology and Professor of Bioengineering and director of the Magnetic Resonance Imaging Center at Caltech. City of Hope investigators include Forman, John Rossi, Ph.D., chair of the Department of Molecular Biology, Andrew Raubitschek, M.D., chair of the Department of Cancer Immunotherapeutics & Tumor Immunology, David Colcher, Ph.D., deputy director of the Division of Radioimmunotherapy Research, Richard Jove, Ph.D., co-director of the Developmental Cancer Therapeutics Program, and Hua Eleanor Yu, Ph.D., professor in the Department of Cancer Immunotherapeutics & Tumor Immunology.

The Keck grant complements work at City of Hope funded through a five-year, $11.5 million Specialized Program of Research Excellence grant from the National Cancer Institute to improve the detection and treatment of Hodgkin’s disease and non-Hodgkin’s lymphoma. That research focuses on developing new, less-toxic therapies derived from molecular and immunologic studies of T-cell and antibody-based therapies, and has already resulted in a phase I clinical trial of T-cell immunotherapy as treatment for lymphoma.

Based in Los Angeles, the W.M. Keck Foundation was established in 1954 by the late W.M. Keck, founder of the Superior Oil Company. The foundation’s grant making focus primarily on pioneering efforts in the areas of medical research, science and engineering.