A novel study describes, the recognition of unique cancer mutations by an approach appears to be responsible for complete cancer regressions in 2 metastatic melanoma patients treated with a type of immunotherapy called adoptive T-cell therapy. And the finding, published in Clinical Cancer Research, moves one step forward to applying immunotherapy into melanoma.

A researcher remarked, “this study provides the technical solution to identify mutated tumor targets that can stimulate immune responses, which is one of the major bottlenecks in developing a new generation of adoptive T-cell therapy. The two targets identified in this study play important roles in cancer cell proliferation.”

Although up to 72% of the patients with metastatic melanoma experienced tumor regression after adoptive T-cell transfer in a clinical trial. However, some patients remained not to benefit. This is because the targets of T cells remains largely unclear. Thus It is important to establish an  efficient approach for target identification.

Investigators used 2 different approach to identify the tumor targets recognized by the clinically effective T cells. First, they used a conventional cDNA library screening to identify nonmutated targets. Second, they used a tandem minigene library screening to identify mutated targets that cannot be found by the conventional screening.

Using cDNA library screening, the researchers identified 3 novel nonmutated tumor targets, and 4 previously known nonmutated tumor targets. Using tandem minigene library screening, they identified 2 novel mutated tumor targets, KIF2C and POLA2, which play important roles in cell proliferation.

Reference:

Efficient identification of mutated cancer antigens recognized by T cells associated with durable tumor regressions. Clin Cancer Res. 2014 Jul 1;20(13):3401-10.