A paper published yesterday in The Journal of Experimental Medicine describes how clinicians based at the Fred Hutchinson Cancer Research Center (WA, USA) successfully treated a patient with metastatic melanoma with a combination of immunotherapies.
The Fred Hutch team combined treatment with blood-derived melanoma-targeting T cells with anti-CTLA4 agent ipilimumab. Alone, both of these therapies demonstrate efficacy in slowing the progression of metastatic melanoma, but complete remissions are rare.
The combination was investigated in a patient of 53 years with multiple melanoma metastases that had demonstrated negligible response to T-cell transfers or ipilimumab treatment. The individual received an infusion of his own antitumor T cells that had been treated with interleukin-21, followed immediately by a dose of ipilimumab.
Within weeks of receiving this combination therapy, the patient’s tumors began to shrink and went on to be eradicated. The paper reports how the individual is still disease free > 5 years later.
The number of antitumor T cells circulating in the patient’s blood in both the short and long term was increased by this combined approach. Moreover, the enhanced immune response induced by this treatment allowed the patient to develop new types of T cells that attacked the melanoma in additional ways, a phenomenon 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,” commented investigator Cassian Yee, now of The University of Texas MD Anderson Cancer Center (TX, USA). “This strategy may hold broad promise for ipilimumab-resistant melanomas.”