T-Cell Therapies Show Promise in Metastatic Melanoma, But Challenges Remain

T-cell therapies show new promise to reshape the landscape of treatment for patients with metastatic melanoma, but practical challenges to manufacture and administrate these drugs in clinics remain a barrier to their effectiveness, according to Dr. Jason J. Luke.

T-cell therapies, like tumor-infiltrating lymphocyte (TIL) therapy, T-cell receptor (TCR) therapy, and CAR T-cell therapy, allow clinicians to create artificial T-cells for immunotherapies to help the body fight cancer cells. For instance, data from a phase 2 trial presented at the 2019 American Society of Clinical Oncology Annual Meeting looking at an investigational TIL therapy showed a 38% objective response rate (ORR) in pretreated patients with metastatic melanoma.

"[T-cell therapy] comes in two flavors. The more immediate therapy is going to involve harvesting TILs, building them up in the lab, and giving them back to patients as a therapeutic modality.” explained Luke in an interview with OncLive®, a sister publication to CURE®. “Further out, we are looking to use engineered cells. Those cells can be T-cell—directed therapies in which we insert a T-cell receptor into a T cell from the patient, as well as CAR T cells, in which we drive a T cell with an enhanced antigen toward the cancer.”

However, while these therapies and data show a potential new path for patients with metastatic melanoma crafting T-cell therapies for patients is a complex process. For example, in TIL therapies patients are required to undergo surgery and the tumor has to be processed in a lab, shipped to a vendor, brought back to the clinic, the patient has to receive chemotherapy prior to the TIL therapy and then the TIL therapy is given, explained Luke. Moreover, for other therapies, like CAR T-cell therapies, large volumes of white blood cells are needed from the patient in order to create the T-cells in a lab. Requiring both an inpatient and outpatient setting for the patient.

"As T-cell therapies come into standard practice, we have to think about what the infrastructure is going to look like in order to actually pull off these kinds of treatments," Luke said. "However, when there is a will there is a way, and when treatments work, we find a way to do it."

Researchers are also hopping to utilize biomarkers in metastatic melanoma to help better utilize T-cell treatments. According to Luke, BRAF mutations and PD-L1 status drive the efficacy of these treatments and allow physicians to understand the likelihood of a patient’s response to treatment. Luke also highlighted new biomarkers clinicians are looking at, like LAG3, and that gene expression in patients with metastatic melanoma is an important field to continue to explore.

“One of the most interesting areas of research in oncology in last few years has been the realization that the contents of the gut or the fecal microbiome can impact patient outcomes,” added Luke when discussing how to predict a patient’s response to treatment. “This is particularly true with regard to immunotherapy in cancer.” For patients with melanoma, researchers are just beginning to understand the relationship of certain bacteria and a patient’s immune response to kick in and fight the cancer.