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Tumor-Infiltrating Lymphocytes ‘Capable of Destroying the Last Cancer Cell’

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Nearly a quarter of patients, 23.7%, treated with adoptive cell transfer tumor-infiltrating lymphocytes for metastatic melanoma have experienced complete and durable responses, according to data presented at ASCO Annual Meeting.

The trial (NCT01174121), conducted by the NCI, has been enrolling patients since 2010, and the subset of patients with metastatic melanoma have shown impressive responses to the therapy over time, with only two complete responders experiencing disease recurrence that resulted in death.

“We have a group of 44 patients with melanoma that are likely cured. They have had no other treatment since their TIL and have been free of disease for more than 5 years,” Stephanie L. Goff, MD, FACS, an associate research physician with the surgery branch at the NCI, told Cell Therapy Next.

Stephanie L. Goff

“TIL[s] appear capable of destroying the last cancer cell,” she added.

Goff detailed the NCI’s experimental treatment, known as ACT-TIL, during the recent ASCO Annual Meeting.

“Our group has been studying the use of tumor-infiltrating lymphocytes for decades, based on early mouse models that demonstrated remarkable tumor regression,” she said. “Careful step-wise inquiry in patients with melanoma led to the current regimen of preparative chemotherapy, cell administration and interleukin-2.

Goff described the process as the passive transfer of activated cells. The regimen, she relayed, begins with excising a portion of the tumor from a patient’s body.

Next, the excised tumor fragments are engineered and cultivated in a laboratory. The excised tumor fragments are grown in high-doses of IL-2 until they form distinct T cell populations. Then the appropriate T cell population for a cancer is expanded using irradiated autologous feeder cells in high doses of IL-2 over a period of 2 weeks.

Finally, the cells are reinfused into the patient who has undergone previous lymphodepletion chemotherapy in the hope that the modified TILs will attack and kill tumor cells. The process is completed by IV interleukin-2 after the cell infusion.

“It’s called adoptive immunotherapy,” Goff said. “It’s the administration of the entire T cell to a patient,” she told the audience at ASCO Annual Meeting.

Overall, 194 patients with metastatic melanoma received treatment with the experimental ACT-TIL protocol at the NCI; a complete response was achieved in 46 patients, partial response in 61 patients and no response in 87 patients.

When asked why ACT-TIL appeared extremely effective in preventing disease recurrence among patients who respond to the therapy, Goff said, in her opinion, different mechanisms may be responsible.

“For some, the last cancer cell was probably eliminated,” she explained. “In others, there may be a small circulating population of T cells that continues immune surveillance.”

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Goff said that the experimental protocol is not for all patients with cancer, but the NCI has a referral team in place that guides clinicians and patients through the trial’s screening process. The team at the NCI’s surgery branch is currently studying ACT-TIL in patients with common epithelial cancers, including colon, breast and lung cancer.

The NCI has been working to commercialize the ACT-TIL protocol for patients with checkpoint inhibitor–refractory melanoma. The protocol is still in the early stages of development for the other cancer types it is currently studying.

With over 12 years of research into ACT-TIL, Goff said that its impact can be felt both in the clinic and as a guide for future research.

“Not only have we learned so much about the capabilities of T cells in the fight against cancer, there are very real people with very real lives that have benefitted from participating in this research,” she concluded. – by Drew Amorosi

Reference:

Goff SL. Tumor infiltrating lymphocytes (TIL) for patients with metastatic cancer. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.

Disclosure: Goff reports no relevant financial disclosures.