Penn researchers receive grant to develop CAR-T for advanced prostate cancer
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Alliance for Cancer Gene Therapy awarded a $500,000 grant to researchers at University of Pennsylvania’s Abramson Cancer Center to develop new chimeric antigen receptor T-cell therapies for advanced metastatic prostate cancer.
The grant recipients include Joseph Fraietta, PhD, assistant professor of microbiology and director of the solid tumor immunotherapy laboratory in Center for Advanced Cellular Therapeutics, and Naomi Haas, MD, associate professor of medicine and director of the prostate and kidney cancer program.
The researchers hope the grant will lead to advances that overcome obstacles associated with using CAR T-cell therapy to treat solid tumors.
“Our long-term goal is to provide [patients with prostate cancer] with treatments that produce safe, effective and durable tumor control,” Fraietta told Healio. “The achievement of success rates with CAR T cells in solid tumors, similar to that seen in hematologic malignancies, would be a major paradigm shift in the therapy of prostate cancer and other incurable nonhematopoietic malignancies.”
The additional funding will enable researchers to explore the metabolic and epigenetic resistance mechanisms inherent with CAR T-cell therapy, Fraietta said.
“By elucidating the effect that nutrient availability has on anticancer epigenetic programing in T cells, such as 5-hydroxymethylcytosine (5hmC) DNA marks, this proposal will ultimately provide a link between nutrient availability in prostate tumors, the loss of [5-hydroxymethylcytosine] marks and antitumor activity of CAR T cells,” he added.
Alliance for Cancer Gene Therapy (ACGT) awarded the grant based on prostate cancer trials being conducted by Haas that use different doses of gene-edited CAR T-cell therapies developed in Fraietta’s laboratory.
“The ACGT Scientific Advisory Council is impressed with the potential of this research team and their successful innovations in the use of T-cell therapy,” Kevin Honeycutt, CEO and president of ACGT, said in a press release. “Because Drs. Fraietta and Haas are building on direct results already achieved with patients, there may be less transition time required to get a promising new treatment into the clinic for [patients with prostate cancer].”
Honeycutt expressed optimism that the research could provide treatment strategies for other solid cancers, including lung, pancreatic, ovarian and brain cancers.
“New cell and gene therapy approaches like the ones Drs. Fraietta and Haas are employing offer new hope to all patients with cancer,” Honeycutt said. “ACGT has been dedicated to funding innovative science that harnesses the power of cell and gene therapy and transforms how cancer is treated.”
The nature of the solid tumor microenvironment and its immunosuppressive mechanisms prevent robust CAR T-cell antitumor activity, Fraietta said.
“A major barrier to the success of CAR T-cell therapy for solid tumors is that the engineered T cells must do battle in a toxic microenvironment that creates a ‘nutrient desert,’ which suppresses T cell function and prevents robust immune responses,” he told Healio.
The Penn research team plans to use genome editing tools, such as CRISPR/Cas9, in addition to novel biomanufacturing strategies, Fraietta added.
“We will create CAR T cells capable of inducing safe, long-term, complete remissions [among] patients with advanced prostate cancer,” he said. “If successful, our proposed studies will undoubtedly provide a tumor-attack roadmap for the treatment of many other cancers, as well, including those of the lung, ovaries, skin, breast, pancreas, brain and so on.” – by Drew Amorosi
For more information:
Joseph Fraietta, PhD, can be reached at Center for Cellular Immunotherapies, Perelman Center for Advanced Medicine South Tower (SPE), University of Pennsylvania, 3400 Civic Center Blvd., Philadelphia, PA 19104-5156; email: jfrai@upenn.edu.
Disclosures: Fraietta reports research funding from Cabaletta Bio, Novartis and Tmunity Therapeutics and consultant roles with Guidepoint Consulting and LEK Consulting, and is listed as inventor on patents licensed by University of Pennsylvania to Novartis.