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Jefferson Research Lab Making Progress In Battle Against Cancer

Patience and Funding Propel Discovery in Use of CAR-T Therapy

For Adam Snook, PhD ’08, it’s all about solving puzzles.

As a basic scientist, Snook seeks to find answers in the laboratory that lead to the development of new therapies for cancer patients.

He admits it’s not always easy.

“I was surprised when I started doing research that it can be a slog at times. We don’t get a lot of wins, and getting great data can be rare,” says Snook, associate professor in the Department of Pharmacology, Physiology, and Cancer Biology in Sidney Kimmel Medical College. “But,” he exclaims with enthusiasm, “when the pieces fall into place, and the data points in the right direction, I love it!”

Lately, those pieces have been falling into place beautifully. Snook, who focuses on basic, translational, and clinical aspects of gastrointestinal biology and tumorigenesis, recently received a $1.3 million grant from the Robert J. Kleberg and Helen C. Kleberg Foundation for his laboratory’s “Universal Cell Therapy for Cancer” study. This research could lead to a powerful new therapy for solid cancers—a therapy that is effective, mass-producible, and affordable.

Snook’s research focuses on CAR-T cell therapy, a form of immunotherapy that has given new hope for those diagnosed with leukemia and lymphoma. In this approach, the patient’s T cells—cells that are part of the immune system—are collected and genetically re-engineered to express a chimeric antigen receptor (CAR), a special protein created in the laboratory that binds to other proteins on cancer cells. The CAR is then added to the T cells and infused into the patient’s vein so that they can attack the cancer cells.

However, says Snook, there are challenges to CAR-T therapy. While it has been curative for some patients with leukemia, it has not been successfully applied to “solid” malignancies such as lung, colorectal, and pancreatic cancers. In addition, it’s time consuming: manufacturing CAR-T cells relies on removing the patient’s own T cells, modifying them in the laboratory over the course of several weeks, and then returning them to the patient. And it is expensive—about $500,000 per treatment.

These limitations mean that the most promising new cancer treatment in decades is not readily available to the majority of cancer patients. In fact, it’s estimated that only 20,000 to 30,000 patients with blood cancers in the United States have been treated with CAR-T cell therapy since it was approved in 2017.

“We don’t have the infrastructure anywhere in the United States to be able to manufacture CAR-T cells one patient at a time for tens or hundreds of thousands of people per year, so we need to find some kind of different approach that will be more easily deployed for many, many patients. And the approach that we’re working on is to use allogeneic donor cells,” Snook explains.

The process includes obtaining T cells from donors, genetically modifying them, then mass producing them to be ready for use on demand for patients in need—almost like blood donation.

Furthermore, continuing to re-engineer the cells could make the treatment safe and effective for a wider range of cancers, as well.

“The CAR-T cell that we’re currently working on also works against many solid cancers,” he says, noting that a paper they are about to publish shows CAR-T cells were effective for the top six causes of cancer death, including lung, pancreas, and breast. “So, we’re merging two areas together so that it will work for many kinds of cancers and would be available for many people at once. It could really shift the outcome for so many patients.”

For example, the lab has identified an enzyme in the intestine called guanylyl cyclase C (GUCY2C), which can be employed as an antigen target for adoptive cell therapy in colorectal cancer. “And we’ve recently discovered its expression by other gastrointestinal cancers, including stomach and esophagus, creating an opportunity to treat these fatal diseases.”

It’s these kinds of encouraging results that keep Snook going, even after more than two decades in the lab. Snook joined Jefferson in 2001 to work on developing vaccines for certain types of cancer; he completed his PhD six years later.

“Some people like to find a new thing; they get bored on one thing for too long. But I really like to be able to take one project and see it through to the end,” he says, noting that his lab has been working on CAR-T cell research for almost a decade. He has also continued the work on a cancer vaccine that he started 23 years ago.

The most recent trial of the cancer vaccine targets colon, pancreas, gastric, and esophageal cancers. Approximately 50 patients have been vaccinated over a period of four years in a phase 2 clinical trial.

“We’ve already seen immune responses in our very first trial with the first version of our vaccine, and we are working toward our next clinical trial—a combination of vaccines that combines the first one with a second,” Snook says.

Snook believes that a vaccine for GI cancers is not too far in the future, noting that “recent studies have produced promising clinical responses with an mRNA vaccine for pancreatic cancer, as well as hopeful results from a trial combining a cancer vaccine with an immune checkpoint blocking drug for melanoma.”

But as always, more research is needed, and funding is critical in all areas of working toward developing therapies in the battle against cancer.

“This Kleberg Foundation grant is huge for us, and now will allow us to really devote a lot more resources to the project overall and hopefully be able to accelerate our pace of development,” he says.

Snook says that grants and funding from private and foundation donors are vital to the success of his—and all—research. Over the past three decades, federal grant money has been increasingly difficult to obtain, so the emphasis has been on smaller pilot grants, grateful patient generosity, and foundations to keep the overall research moving forward.

With enough funding and enough research, Snook believes curing cancer in our lifetime is possible.

“We have made fantastic progress overall in the treatment of cancer. Things like childhood cancers went from 80 percent fatal to 80 percent curable over the last 50 or 60 years,” he says. “And about five years ago we actually started to see a decline in cancer death rates, mostly due to improvements in lung cancer treatment with immunotherapy. We’re making big progress in some areas and slower progress in others, but overall, we keep making advances and improving patient outcomes.” And those advances will spur his lab on to continue its work until all of the pieces of the puzzle are together and cancer is cured.