Scientists have developed a novel synthetic DNA vaccine to target multiple members of a family of proteins that are overexpressed in several types of cancer. According to their paper, published in Clinical Cancer Research, the strategy was effectively tested in a mouse model of melanoma.

MAGE-A protein expression is restricted to tumor cells and present in a wide range of cancers, making them a promising target for immunotherapy. In spite of this, prior trials of cancer vaccines targeting the MAGE-A3 member, which has the highest expression in several solid tumors, have thus far been unsuccessful.

Looking to overcome this issue, scientists at The Wistar Institute performed a thorough analysis of expression levels of all twelve proteins in the MAGE-A family in human cancers using RT-qPCR. They observed that many of the MAGE-A members are highly expressed in tumor cells in several cancer types, with many tumors showing expression of several MAGE-A members simultaneously. This indicated that previous vaccines may have failed due to their limited scope—targeting just one type of MAGE-A protein would not be effective in driving strong T-cell immunity due to development of immune tolerance.

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Using a combination of structurally relevant primary sequences from multiple MAGE-A members, the researchers created a hybrid vaccine, capable of targeting several MAGE-A family members simultaneously. When tested in a mouse model of melanoma, the vaccine elicited a much more robust CD8+ T cell-mediated immune response, slowing tumor growth and prolonging survival.

"Our cross-reactive vaccine has a significant advantage in preventing tumor escape compared to previously designed MAGE-A3-specific vaccines," said Elizabeth K. Duperret, Ph.D., postdoctoral fellow in the Weiner Lab and first author on the study. "Patients whose tumors express multiple members of this family of antigens represent an important group to study the benefits of this immunotherapy approach." The particular vaccine approach could have further applications beyond the MAGE-A family of proteins.