Multiple Grants Generate Momentum in Cancer Research

Research efforts to improve outcomes for people with ovarian cancer or glioma just got a boost in excess of $3 million.

Noriyuki Kasahara, M.D., Ph.D., a researcher at Sylvester Comprehensive Cancer Center and professor of biology and pathology at the University of Miami Miller School of Medicine, and colleagues have developed a unique technology to deliver targeted chemotherapy. Their strategy focuses on using retroviral replicating vectors (RRVs) to deliver prodrug activator (“suicide”) gene therapy into tumors.

“I was very happy to recently receive notice of a new grant award, an R01 research grant from the National Cancer Institute at NIH, totaling $2.6 million in direct and indirect costs over five years,” Kasahara said.

The award is a nod to his previous work and a new project applying RRV technology to ovarian cancer that he has initiated at the Miller School of Medicine in collaboration with Brian Slomovitz, M.D., chief of gynecologic oncology at Sylvester. This funding will enable Slomovitz and study co-investigators Xiangxi “Mike” Xu, Ph.D., professor of cell biology, and Tan A. Ince, M.D., Ph.D., scientific director of Sylvester’s Live Tumor Culture Core and Tissue Bank Core Facility, to continue applying this RRV-mediated suicide gene therapy approach to ovarian cancer, and to test treatment regimens that combine gene therapy with immunotherapy in this disease.

Additional Funding

Kasahara also just received a $500,000 clinical translation grant from the Alliance for Cancer Gene Therapy (ACGT) to develop a next-generation RRV for cancer gene therapy. This grant will enable Kasahara to further evaluate a new RRV to deliver another, different prodrug activator gene in glioma models, and pursue preclinical validation to support clinical application in the near future. This “suicide” gene kills cancer cells through a different mechanism than Toca 511, the RRV co-developed by Kasahara and a biotech venture, Tocagen Inc., which is currently being evaluated in Phase IIB/III clinical trials for recurrent high-grade glioma.

In addition, Kasahara has just been awarded a Florida Academic Cancer Center Alliance grant totaling $100,000, shared with Dr. Peter Forsyth, chair of neuro-oncology at Moffitt Cancer Center, for pilot studies to combine oncolytic virotherapy using myxoma virus with suicide gene therapy using RRV.

“In the future, there is potential to administer both of these RRVs for combination gene therapy — analogous to combination chemotherapy, but generated directly within the tumor itself,” Kasahara said, “as well as to co-administer these two different viruses which can attack cancer cells in different ways.”

Expanding the Promise of Gene Therapy

The FDA also recently granted Tocagen, Inc., the University of Miami’s biotech partner on the RRV research, approval to start a new Phase I clinical trial to evaluate intravenous delivery of the RRV currently in clinical development, Toca 511, for treatment of various other systemic cancers.

“This new clinical trial is headed by Dr. Jaime Merchan here at the University of Miami, and will evaluate Toca 511 prodrug activator gene therapy in colorectal cancer, pancreatic cancer, as well as metastatic renal cancer, lung cancer, melanoma, and — based on validating data from our new preclinical studies conducted at UM — now also ovarian cancer,” Kasahara said. “Our university is the first in the nation to initiate this clinical trial.”

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