Arming CAR T cells for the solid tumor battlefield.

“I absolutely love my job!” says Joseph Fraietta, PhD. “It’s about the people – the patients and their lives and their families.” 

Dr. Fraietta recalls being in grad school, working in infectious disease and HIV immunology, and reading about the game-changing CAR T-cell therapy developed by Alliance for Cancer Gene Therapy Research Fellow Carl June, MD. “I love thinking about cell and gene therapies as living, replicating drugs,” says Dr. Fraietta. “It’s beyond exciting to think a patient could receive a one-time infusion and that’s it! The pace of progress is even more exciting. A lot of what’s happening in laboratories these days is rapidly translating into curative therapies that extend life and improve quality of life for cancer patients.” 

Down the hall from Dr. June at the University of Pennsylvania Perelman School of Medicine (Philadelphia, Pa.), Assistant Professor of Microbiology Dr. Fraietta and his colleagues are using a grant from the Alliance for Cancer Gene Therapy to improve the success rates of CAR T-cell therapies for patients with solid tumors and very dismal prognoses. 

“We know CAR T-cell therapy is successful in demolishing many blood cancers,” says Dr. Fraietta, “but there are barriers to their success in solid tumors. The first barrier is delivering them to the tumors (getting them to be able to identify the cancer), then enabling them to break through the tumor’s stromal compartments to gain access to the inside of the tumor, and ultimately, to stay alive and well long enough to demolish the tumor.” This third barrier is the target of Dr. Fraietta’s current research. 

“A tumor’s microenvironment is a hostile sewer,” says Dr. Fraietta. “It suppresses a person’s natural immune system in many ways. For genetically engineered T cells, it’s a nutrient desert. Once inside a tumor, T cells starve and can’t function. My vision is to gain an actionable understanding of how a tumor’s microenvironment dooms the fate of T cells and then use that knowledge to overcome those threats.” 

Dr. Fraietta’s work combines and builds on past insight he and his team developed and published in the scientific journals Nature and Molecular Therapy. His partner in progress for this latest venture is Naomi Haas, MD, an expert in the field of prostate and kidney cancer. While Dr. Haas leads clinical trials for different immune therapies, Dr. Fraietta is working in the laboratory to better prepare CAR T cells for the solid tumor battlefield. 

“I always wanted to do something that was aggressively translational, something that could make a real difference in people’s lives,” says Dr. Fraietta. “Today I’m lucky to be living at a time when I can realistically do this. I work with an amazing, interdisciplinary team of professionals and we’re experiencing a monumental paradigm shift in medicine.” 

“Back in the 1890s,” says Dr. Fraietta, “a young surgeon at New York Memorial Hospital named William Coley treated a patient with a severe bacterial infection. In the process, he discovered his treatment also cured the patient’s cancer! Here we are 100 years later, and thanks to the hard work and perseverance of many tenacious pioneers, we’re witnessing a revolutionary emergence of immune therapy as a transformational treatment protocol for cancer. There’s nothing better than when we get to interact with patients for whom cell or gene therapy is proving successful.”