Identifying specific neo-antigens in melanoma, a cancer known for having high numbers of genetic mutations caused by exposure to ultraviolet light, is no easy task. A melanoma biopsy typically carries 500 or more mutated genes.
To date, vaccines have targeted non-mutated shared proteins expressed in normal and cancer cells. This has made it difficult to stimulate a robust immune response because the immune system does not see these proteins as foreign, said senior author Gerald Linette, M.D., Ph.D., a Washington University medical oncologist.
Researchers recently published results on the first human study1 looking at personalized vaccines designed to activate T-cells aimed at individual cancer patient’s mutations. The study, including three advanced melanoma patients, suggests these tailor-made vaccines boost T-cell number and diversity, resulting in a tumor response.
The vaccines in this study are engineered based on which of the tumor-specific proteins altered due to DNA mutations are most likely to elicit a strong individual immune responses, according to co-author Elaine Mardis, Ph.D., co-director of the McDonnell Genome Institute at Washington University.
“In particular, our vaccine approach seeks to remind the patient's immune system that these mutated proteins are truly non-self…,” Mardis said.