Editors' ChoiceCancer

Tailor-made T cells for cancer therapy

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Science Translational Medicine  19 Jul 2017:
Vol. 9, Issue 399, eaao0968
DOI: 10.1126/scitranslmed.aao0968


Investigators from two teams have created personalized vaccines for the treatment of melanoma by identifying tumor-specific neoantigens.

Immunotherapy, in which the body’s own defense system is stimulated to fight disease, is a highly promising approach for treating cancer. Two recent publications, from groups working independently, describe clinical trials for melanoma in which personalized immunotherapies were used to treat mutations specific to the individual patients enrolled in the studies. In each of the trials, researchers sequenced the DNA of melanoma cells and identified mutation-specific neoantigens, or molecules that are unique to cancerous cells and displayed on the cell surface. Neoantigens can be recognized by T cells, specifically targeting the cancer cells for destruction. Multiple neoantigens were computationally predicted and used to create vaccines that were tailored to the unique mutations found in each patient’s cancer cells.

The method of inoculation differed in the two trials, but both studies resulted in highly promising outcomes. In one trial, from Ott et al., patients were inoculated with clinical-grade synthetic peptides, whereas Sahin et al. delivered an RNA vaccine to the patients’ lymph nodes. Both studies resulted in highly encouraging outcomes, with production of T cells that recognized tumor neoantigens and were able to discriminate melanoma cells from healthy cells. Patients had a decrease in tumor size, reduction in the rate of recurrence of metastatic events after the therapy compared with the period before inoculation, and increase in survival. In some patients, the vaccination alone was not sufficient to treat the melanoma but produced complete regression in conjunction with other treatments.

This personalized approach was multipronged, with several neoantigens used for each patient, enabling efficient treatment for highly heterogeneous cancers. Although the treatment was not successful in all participants, these studies were conducted in high-risk groups of patients and may be more successful in earlier stages of the disease or in conjunction with currently existing therapies. Together, these results indicate that mutation-specific vaccines for the treatment of melanoma are safe, hold promise for the treatment of melanoma and other types of cancers, and may in fact be better than a one-size-fits-all approach to cancer treatment.

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