The VOICE of UPMC Shadyside Winter 2022–2023

At the Frontier of Truly Personalized Medicine

Developing One of the Leading TIL Cell Therapy Programs in the United States

Four years ago, Udai S. Kammula, MD, came to UPMC Hillman Cancer Center with a very ambitious goal: to develop novel and transformative cell therapies for patients with some of the toughest metastatic cancers that exist — and to treat those patients in clinical trials at UPMC Shadyside. Now Dr. Kammula, a scientist, surgical oncologist, and director of Hillman’s Solid Tumor Cell Therapy Program, has developed one of the leading TIL cell therapy programs in the United States. 

“TIL, or tumor-infiltrating lymphocyte, cell therapy is a very specialized form of cancer immunotherapy,” Dr. Kammula explains. “Tumor-infiltrating lymphocytes, or T-cells, are white blood cells that have the ability to recognize and kill cancer cells. In the TIL therapy process, these cells are removed from the patient’s body in trials we have developed at Shadyside, then grown and expanded in number and sometimes genetically altered in our laboratory across the street at Hillman. And then we primarily infuse the cells as a cancer treatment. 

TIL therapy enhances what nature has already started. Instead of waiting for an immune system to be generated, they’re actually installing an immune system. Many have given this approach the moniker of administering a living drug.
- Udai S. Kammula, MD

“There are not very many centers around the country or the world that are conducting these types of studies,” Dr. Kammula states. “What makes our group very different is that when we remove the T-cells, we ‘interrogate’ them and can select TIL with significant personalized anti-tumor reactivity. We pick the cream of the crop, and then we expand those for patient delivery. There are no two TIL products that are exactly the same. Each one is unique. This is both the beauty of it and the challenge of it. 

“And we use those cells as the drug, as the treatment,” Dr. Kammula says. “By activating TIL cells ex-vivo, outside the body, they are free from the potentially suppressive tumor microenvironment. So they get infused back into the patient as the primary therapy to treat solid tumors that have spread throughout the body. Once infused back into the patient, the TIL continue to multiply, recognizing and killing cancer cells.

“When you give billions of highly activated and, in fact, hungry T-cells all at one time, we see tumor responses rather quickly,” continues the doctor. “We literally can see these tumors shrinking by the end of a week. And if they do continue to show regression, we don’t do anything. We know that we’ve implanted these seeds. We let them do their job.

“So TIL therapy enhances what nature has already started,” continues Dr. Kammula. “Instead of waiting for an immune system to be generated, they’re actually installing an immune system. Many have given this approach the moniker of administering a living drug.”

“I prayed every night”

While CAR T (chimeric antigen receptor) T-cell therapy has been used most effectively against blood cancers, TIL therapy was originally developed to fight advanced skin melanoma. Dr. Kammula’s team has expanded TIL therapy to treat other challenging solid tumors such as advanced pancreatic cancer, mesothelioma, and uveal melanoma. 

Back in 2017, Debra Miller, a psychiatric social worker, was diagnosed with leiomyo-sarcoma, a rare cancer that grows in the smooth muscles, including the intestines, stomach, bladder, and blood vessels. After three rounds of chemotherapy and multiple surgeries, her cancer continued to spread.

“When I first started this journey, there were no clinical trials for this type of cancer,” she said in a UPMC video. “I prayed every night that there would be some kind of breakthrough, something — and then this [TIL therapy] happens.”

After a small sampling of her TIL cells were removed and expanded in the lab, she underwent lympho-depleting chemotherapy — in order to transiently wipe out her immune system so that it could be built back up again with the new cells. Dr. Kammula uses the analogy of curing a computer virus by wiping your hard drive clean and starting over. 

“I think it’s going to be neat no matter what my outcome is,” Ms. Miller said of the clinical trial. “And if somebody can benefit from this type of research that’s being done on me, then I’m happy for that.”

After her expanded, highly personalized cells were reinfused, Ms. Miller returned to work. “She’s got such an inspiring outlook,” says Mary Kate Ayers, RN, MSN, OCN, senior clinician at UPMC Shadyside who works with Dr. Kammula. 

Along with other oncology nurses, Ms. Ayers finds a lot of satisfaction in safely and compassionately caring for patients participating in these trials. “Because this therapy is so new and rare, we are the ones who are developing the standards of care for managing these patients,” she says. “People have come to Shadyside from around the world to take part in the treatment. 

“My late grandfather was an oncologist,” Ms. Ayers reflects. “I would love to be able to talk to him about how we care for cancer patients today compared to 50 years ago. He would be so amazed.

“And I have nothing but lovely things to say about Dr. Kammula,” she adds. “I really appreciate his attention to detail and how closely he monitors his patients. He is always very supportive of the nursing staff and accessible to us 24/7 if we ever have a concern or question.”  

Dr. Kammula says that about 50 patients have been treated in clinical trials at Shadyside, “and we’re seeing responses even in cancers that are highly refractory. We’re now researching whether this therapy is going to be effective for different types of cancer. We’re also exploring ways in which bioengineering and gene therapy could be used to improve the process.” 

Dr. Kammula appreciates the “unique, really collaborative effort between Hillman Cancer Center and Shadyside Hospital. That’s what drew me here from the NIH — because that’s the NIH model, with the laboratories right next to the patient care.

“Every single day I come to work is an exciting day,” he says, “because we’re going places that no one has ever gone before.”

Because this therapy is so new and rare, we are the ones who are developing the standards of care for managing these patients. People have come to Shadyside from around the world to take part in the treatment.
- Mary Kate Ayers, RN, MSN, OCN