New Immunotherapy Approach Shows Activity in NCI Trials

Treatment with tumor-infiltrating lymphocytes (TILs), a new type of immunotherapy, induced complete remission in a patient with breast cancer, according to a report by Steven A. Rosenberg, MD, PhD, and researchers from the National Cancer Institute (NCI) published in Nature Medicine. The investigational therapy is a modified method of adoptive cell transfer (ACT), which has previously demonstrated efficacy in treating melanoma and other types of cancer with high levels of somatic mutations.

“[With TILs], we’ve developed a highthroughput method to identify mutations present in a cancer that are recognized by the immune system,” Dr. Rosenberg said in an NCI press release. “This research is experimental right now. But because this new approach to immunotherapy is dependent on mutations, not on cancer type, it is in a sense a blueprint we can use for the treatment of many types of cancer.”

The form of ACT being evaluated in the ongoing phase II trial uses a patient’s own TILs, manufactured to specifically target tumor cell mutations, then infused back into the patient’s body.

In the report published recently, a woman with previously treated, metastatic breast cancer underwent DNA and RNA sequencing to identify mutations unique to her cancer. Next, the researchers tested different TILs from the patient and selected those that recognized one or more of these mutations. The investigators found that TILs recognized mutant versions of four proteins (SLC3A2, KIAA0368, CADPS2, and CTSB).

“Adoptive transfer of these mutant protein–specific TILs, in conjunction with [pembrolizumab], mediated the complete durable regression of metastatic breast cancer, which is now ongoing for more than 22 months,” the authors reported.

“This is an illustrative case report that highlights, once again, the power of immunotherapy,” said Tom Misteli, PhD, director of the NCI’s Center for Cancer Research. “If confirmed in a larger study, it promises to further extend the reach of this T-cell therapy to a broader spectrum of cancers.”

Source: National Institutes of Health press release, June 4, 2018; Zacharakis N, Chinnasamy H, Black M, et al. Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer. Nat Med. 2018;24:724-30.