A patient with refractory metastatic melanoma was successfully treated with a novel combination of 2 different types of immunotherapy.1
Melanoma is the most deadly form of skin cancer, accounting for the overwhelming majority of deaths from skin cancer once it metastasizes to other tissues in the body. Frequently, treatment of metastatic melanoma involves enhancing the immune system’s ability to destroy the tumor.
Isolation of a pure population of the patient’s own T cells, a type of immune system cell, followed by administration of that population back to the patient can allow the T cells to target the disease. Another immunotherapy option is treatment with ipilimumab, an antibody that can activate the patient’s existing T cells by inhibiting the function of a protein called CTLA4.
Both treatments can slow the progression of metastatic melanoma, but usually neither therapy can result in complete remission. Researchers wondered if combining the treatments could yield better results.
This study, published in the Journal of Experimental Medicine, tested the combination of immunotherapies on a patient with multiple metastases who had previously experienced little response to either T cell transfers or ipilimumab therapy.
The male patient was age 53 years and received an infusion of his own T cells followed immediately with a dose of ipilimumab. The T cell infusion was treated with interleukin-21, an immune system protein that promotes T cell survival.
The patient’s tumors began to shrink within weeks. Eventually, the tumors disappeared completely. More than 5 years later, the patient remains completely disease-free.
This combined approach increased the amount of antitumor T cells circulating in the patient’s bloodstream in both the short and long term. In addition, the heightened immune response stimulated by this treatment resulted in the development of new types of T cells that attacked the tumors in other ways. This phenomenon is known as epitope spreading.
“Combining CTLA4 blockade with the transfer of well-characterized, robust antitumor T cells represents an encouraging strategy to enhance the activity of the adoptively transferred T cells and induce antitumor responses,” said senior author Cassian Yee, MD, who executed this research when he was in the Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, Washington.
“This strategy may hold broad promise for ipilimumab-resistant melanomas.”
1. Chapuis AG, Lee SM, Thompson JA, et al. Combined IL-21-primed polyclonal CTL plus CTLA4 blockade controls refractory metastatic melanoma in a patient [published online May 30, 2016]. J Exp Med. doi:10.1084/jem.20152021