T Cell Immunotherapy an Improvement Over Checkpoint Inhibition

Researchers here report on the results of a phase III trial of tumor infiltrating leukocyte (TIL) therapy for melanoma. A patient's T cells are multiplied outside the body and then injected, along with chemotherapy beforehand to clear existing T cell populations, and IL-2 delivery afterwards to promote replication of the delivered T cells. It has meaningful side-effects, as do other cancer immunotherapies, but the outcome is an improvement over the present standard approach of checkpoint inhibition for melanoma. Even as better approaches to cancer therapy are in development, such as those based on interference in telomere lengthening, we should expect to see continued iteration and improvement in immunotherapies.

Melanoma is an aggressive type of skin cancer. Ten years ago, metastatic melanoma was almost certainly a death sentence within a year after diagnosis. "Ten years ago, melanoma had such a bad prognosis that I would be seeing an entirely new patient population every year - but now I've been seeing some patients for ten years. This is largely due to the discovery of immunotherapy, which has revolutionized treatment for melanoma. But we still see that about half of the people diagnosed with metastatic melanoma succumb within five years, so we're still not where we want to be - not at all."

TIL stands for tumor-infiltrating lymphocytes: immune cells, T cells in this case, that have entered the tumor. The body trains these T cells to recognize and then kill foreign invaders, such as tumor cells. The presence of T cells in a tumor is a good sign, because it means that the immune system has recognized the tumor as a foreign entity and wants to attack and destroy it. Many tumors, however, do not contain enough potent T cells. TIL therapy aims to multiply the patient's T cells, which are isolated from one of the tumor sites, into a huge army consisting of billions of T cells.

Researchers started an international trial in 2014: the TIL trial, which compared TIL therapy to standard immunotherapy with the checkpoint inhibitor ipilimumab. The results of the TIL trial have now been presented. In almost half (49%) of the patients with metastatic melanoma who received TIL therapy, the metastases had decreased in size. In 20% of patients, the metastases had even disappeared completely. This also proved to be the case in patients who had already received prior treatment at the time of their participation in the trial. These percentages were significantly higher compared to those seen in the patient group receiving standard immunotherapy (ipilimumab). In the ipilimumab group, metastases had decreased in size in 21% of patients, and in 7%, the metastases had disappeared completely.

The progression-free survival, the percentage of patients who do not experience disease progression after a specified time period, was 53% after six months for patients receiving TIL therapy, and 21% in the control group (ipilimumab). At a median follow-up time of 33 months for all patients, the median progression-free survival of patients who had received TIL therapy was significantly better (7 months) than that of patients treated with ipilimumab (3 months).

Link: https://www.nki.nl/news-events/news/patient-s-own-immune-cells-effective-as-living-drug-for-melanoma/