Highlights:
- A novel clinical tool discovered to predict patients’ response to therapy.
- Scientists took patient cells, expanded them, and reinfused back into patient to target cancer.
- Adoptive T cell therapy successfully treats metastatic uveal melanoma.
Immunotherapy is a form of treatment given to patients in which the immune system is activated to target the infection or pathogen. In many cases, specifically cancer, the body’s immune system cannot recognize the disease. These tumors are known to be ‘immunologically cold’. The goal of immunotherapy is to trigger the immune system to detect these ‘cold’ tumors and make them ‘immunologically hot’. For the last decade, immunotherapy has advanced the field in cancer treatment. As a result, in 2018 two researchers, Drs. James Allison and Tasuku Honjo, were awarded the Nobel Prize in Physiology or Medicine for their work on immune checkpoint inhibitors, a successful form of immunotherapy.
There are various types of immunotherapies. One includes Tumor infiltrating lymphocytes (TILs). This specific therapy takes the T cells, a type of immune cell responsible for lysing or killing cancer cells, from the patient and grows them in a laboratory. The specific T cells regenerated are those that can recognize and target the tumor. Once the cells are expanded, they are then reinfused back into the patient to initiate a strong wave of immunity against the cancer. This therapy has made significantly strides in cancer treatment and was Food and Drug Administration (FDA) approved this year for solid tumors, specifically melanoma.
A recent study that came out in Nature Communications, by Dr. Udai Kammula and his team found that TIL therapy successfully treated patients with a rare eye tumor, known as metastatic uveal melanoma. Kammula is Associate Professor and Director of the Solid Tumor Cell Therapy Program at UPMC Hillman Cancer Center at the University of Pittsburgh. His research focuses on cancer immunotherapy including adoptive T cell transfer, tumor-infiltrating lymphocytes, and gene therapy. Kammula and his team also developed a new technique to predict which patients are more likely to respond to immunotherapy.
Uveal melanoma begins in the eye, but quickly spreads throughout the body including the liver. Due to the fast rate of metastasis, this cancer is very difficult to treat. The team analyzed a large repository of uveal melanoma samples and found the samples to be filled with T cells. As a result, researchers demonstrate that T-cells are getting to the tumor, but because of the suppressive characteristics of the tumor and environment around it, the cells aren’t being activated. TIL immunotherapy was able to activate these cells to successfully target the tumor.
Although TIL therapy is extremely effective, it is not as successful in some patients. This is mostly due to the progressed state of melanoma and the genetic makeup of the tumor. To determine which patients should receive this therapy, researchers generated a tool called Uveal Melanoma Immunogenic Score (UMIS). This score measures over 2,000 genes expressed by the tumor and immune cells in a patient. The higher the score, the more TILs a patient has and the more likely the treatment will effectively target the tumor. Consequently, patients with a high UMIS, had better clinical outcomes with TIL therapy. Overall, Kammula and his team found that TIL therapy can effectively treat uveal melanoma and found a way to predict response in patients. This work reduces the severity of uveal melanoma and significantly improves patient survival.
Study, Nature Communications, Udai Kammula, UPMC Hillman Cancer Center, University of Pittsburgh