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OHSU offers new treatment for deadly skin cancer

OHSU Knight Cancer Institute only provider in the region to offer TIL therapy for late-stage melanoma; holds promise for other types of cancer
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Richard Maziarz, M.D., medical director of the adult blood and marrow stem cell transplant and cellular therapy program at the OHSU Knight Cancer Institute. Researchers in the program are looking for new ways to treat lethal cancers such as skin cancer. (OHSU/Kristyna Wentz-Graff)
Richard Maziarz, M.D., medical director of the adult blood and marrow stem cell transplant and cellular therapy program at the OHSU Knight Cancer Institute. Researchers in the program are looking for new ways to treat lethal cancers such as skin cancer. (OHSU/Kristyna Wentz-Graff)

The OHSU Knight Cancer Institute is now offering a new treatment for people with late-stage melanoma, a deadly type of skin cancer that kills roughly 8,000 Americans every year.

The new treatment, known as tumor-infiltrating lymphocytes therapy, or TIL therapy, harnesses the power of the human immune system to seek out and destroy cancer cells.

In February, the Food and Drug Administration approved TIL therapy for people with late-stage melanoma that continues advancing after other treatments have failed.

TIL therapy, which is also known as lifileucel, or Amtagvi, is a type of so-called “living medicine” derived from a patient’s own blood cells. Oregon Health & Science University is the only hospital in the Pacific Northwest authorized to offer it.

In the future, researchers think TIL therapy may also hold promise for other types of cancer, such as colorectal cancer and non-small-cell lung cancer.

Richard Maziarz, M.D., in a blue shirt, smiling.
Richard Maziarz, M.D. (OHSU)

“This is an important breakthrough,” says immunotherapy expert Richard Maziarz, M.D., professor of medicine in the OHSU School of Medicine and medical director of the cell therapy program at OHSU. “It’s a major deal for people with melanoma, and in the future, it’s likely to prove to be a big deal for people with other types of cancer.”

A lethal cancer

Sancy Leachman, M.D., Ph.D., wearing a white coat, smiling.
Sancy Leachman, M.D., Ph.D., (OHSU)

Melanoma is a lethal type of skin cancer that strikes about 100,000 Americans every year. It’s easy to treat so long as it’s detected soon enough, says Sancy Leachman, M.D., Ph.D., professor of dermatology in the OHSU School of Medicine and director of the melanoma program at OHSU.

“Most of the time, we catch it early and cut it out,” she says.

Unfortunately, if it’s not caught early, melanoma can quickly metastasize, or spread to other parts of the body.

“Melanoma is one of the most aggressive tumors on the planet,” Leachman says. “Once it spreads, it’s very difficult to treat.”

In recent years, newer treatments such as checkpoint inhibitors and targeted therapy have helped some people with metastatic melanoma. But many others still die from the disease.

“If you develop metastatic melanoma, you have less than a 50-50 chance of being alive in five years, no matter what treatment you get,” Leachman says. “That’s what’s so exciting about TIL therapy. Now we can change those odds.”

Immune warriors

TIL therapy is a living medicine derived from a patient’s own cells. It relies on lymphocytes, which are white blood cells often described as the soldiers of the immune system. These cells roam the body, in and out of the bloodstream, hunting for infectious pathogens, cancer cells and anything they don’t recognize as belonging. When they find a tumor, the lymphocytes gear up for action. They latch on to the surface of the tumor cell, activate, penetrate a tumor nodule and attack the cancer cells within. These tumor-infiltrating lymphocytes, as they are now known, are highly effective at recognizing and destroying cancer cells.

“The ones that get through are real warriors,” Maziarz says. “They are specifically targeted to kill that cancer.”

However, tumors can fight back. They can issue biochemical signals that confuse the TILs and starve them of nutrients. The TILs run out of energy and go inert, which lets the tumors grow and spread.

TIL therapy is a way to recharge the immune system. Surgeons remove a small piece of a patient’s tumor that contains exhausted TILs. They chill the sample to keep the cells alive and send it off to a lab where the TILs are isolated, cultured, reinvigorated and cloned. After several weeks, doctors infuse the patient with billions of living, rejuvenated TILs.

“When these cells see the cancer, they bind to it and begin to kill immediately,” Maziarz says.

The treatment is demanding: Patients undergo surgery, chemotherapy and immunosuppression. Treatment and recovery can take 10 weeks from start to finish. But results from experimental trials have been encouraging: The C-144-01 study followed 153 patients with late-stage melanoma who had all tried other treatments without success. After undergoing TIL therapy, 41% remained stable or saw modest improvement, and 31% saw dramatic improvement — in some cases, their tumors disappeared altogether.

“If it works, the tumor cells can be completely eliminated,” Leachman says. “It’s brilliant.”

Future potential

Researchers have been trying to harness the power of TILs since the 1980s, when a team at the National Cancer Institute published promising early results.

John Vetto, M.D., wearing a suit and tie, smiling.
John Vetto, M.D. (OHSU)

Surgical oncologist John Vetto, M.D., professor of surgery and dermatology in the OHSU School of Medicine, was part of that team, and has worked on many studies over the years to see how TILs could be used to treat melanoma and other types of cancer.

“It is very exciting for me personally to see TIL make the long road from bench to patient bedside and to have had a small part in that history,” Vetto says. “It has been especially gratifying to see the science refined, the process streamlined, and the potential clinical benefit become a reality for those afflicted with advanced melanoma.”

Maziarz, who was on a video call with colleagues, actually cheered when he heard the news that the FDA had granted approval.

“As a trained molecular immunologist, I’ve been waiting for this moment for almost 40 years,” he says.

Iovance Biotherapeutics, which manufactures Amtagvi, has teamed up with OHSU and a handful of hospitals nationwide with the knowledge and expertise to offer the therapy to patients.

In the meantime, Maziarz, Leachman and Vetto look forward to a time when the treatment may be offered to people with other types of cancer.

“This treatment is in rapid evolution,” Leachman says. “What that means is that it will get better and better. More targeted. Less toxic. This is a whole new type of therapy that we didn’t have before.”

OHSU expects to begin offering TIL therapy to patients with metastatic melanoma in March 2024.

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