The California Institute for Regenerative Medicine (CIRM) has awarded City of Hope nearly $32.6 million in grants for research into potential therapies for AIDS-related lymphoma and brain cancer.

Robert Klein, chair of the California Institute of Regenerative Medicine’s governing board, announces research grants. (Photo courtesy California Institute of Regenerative Medicine)

Karen Aboody, M.D., associate professor in the Department of Neurosciences and Division of Neurosurgery, will lead an $18 million study to research a novel treatment for glioma. A $14.6 million grant will support John Zaia, M.D., the Aaron D. and Edith Miller Chair in Gene Therapy and professor of virology, and his team, who are pursuing an AIDS-related lymphoma treatment that may provide patients with permanent immunity to HIV.

Both four-year grants were announced Oct. 28. City of Hope investigators will collaborate on three additional new CIRM grants, as well. City of Hope garnered about 14 percent of the grants awarded.

Aboody’s grant focuses on high-grade glioma, an aggressive brain cancer. Aboody was one of the first researchers to demonstrate that neural stem cells migrate to invasive brain tumors. Her team uses tumor-targeting neural stem cells to deliver cancer-killing agents specifically to these tumors.

The study aims to further refine the therapeutic potential of this technology, which has been submitted to the Food and Drug Administration for investigational new drug status, the first step in getting a new drug or treatment approved.

Co-principal investigators on the grant include Larry Couture, Ph.D., senior vice president of the Sylvia R. and Isador A. Deutch Center for Applied Technology Development, and Jana Portnow, M.D., assistant professor of medical oncology. City of Hope will collaborate with Childrens Hospital Los Angeles on the study.

Zaia’s team will investigate a potential HIV-lymphoma therapy that builds on an approach created by John J. Rossi, Ph.D., Lidow Family Research Chair in molecular and cellular biology. Zaia’s application for the CIRM Disease Team Research Awards received the highest evaluation score among all competing submissions in this round of funding.

The study grew out of City of Hope’s influential studies into the use of hematopoietic cell transplantation, or HCT, to treat patients with HIV and AIDS-related lymphoma. HCT today is a widely used therapy option for lymphoma patients — but for patients who are HIV-positive, it may provide another benefit: new, uninfected blood stem cells that could reboot an HIV-weakened immune system.

However, noted Zaia, “one of the most difficult obstacles to achieving success with HCT treatment is the resilience of HIV, which can resurge and once again destroy the immune system through any virus that hides away in the lymph nodes.”

Researchers have shown that a natural CCR5 gene mutation in certain people imparts resistance to HIV infection. The new method under investigation targets the CCR5 gene with a zinc finger nuclease, cutting the gene permanently. That results in a nonfunctioning protein, potentially conveying HIV resistance in the new immune system created through HCT.

The CIRM grant will support the research team’s efforts to create an efficient manufacturing process for the therapy. The team intends to submit an investigational new drug application by 2013.

Sangamo Biosciences Inc. developed the therapy. Research team members include David DiGiusto, Ph.D., professor in the Department of Cancer Immunotherapeutics and Tumor Immunology, and Amrita Krishnan, M.D., director of the Multiple Myeloma Program in the Department of Hematology & Hematopoietic Cell Transplantation, as well as Rossi and Couture.

The team also includes researchers from the Keck School of Medicine of the University of Southern California (USC).

In addition, Couture is participating in three other studies that received CIRM grants. He will oversee manufacturing of therapies for a different HIV study focusing on RNA interference and a sickle cell disease study, both led by the University of California, Los Angeles, as well as therapy for an age-related macular degeneration study led by USC.