Mutation-specific control of BCR-ABL T315I positive leukemia with a recombinant yeast-based therapeutic vaccine in a murine model

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• 作者：Melanie R. Bui ; Victoria Hodson ; Tom King ; Derek Leopold ; Shaodong Dai ; Valerie Fiolkoski ; Sarah Oakes ; Richard Duke ; David Apelian ; Alex Franzusoff ; James DeGregori
• 关键词：T315I ; BCR-ABL ; Immunotherapy
• 刊名：Vaccine
• 出版年：2010
• 出版时间：23 August 2010
• 年：2010
• 卷：28
• 期：37
• 页码：6028-6035
• 全文大小：1263 K

文摘

Chromosomal translocations generating the BCR-ABL oncogene cause chronic myeloid leukemia (CML) and a subset of acute lymphoblastic leukemia. The BCR-ABL^T315I mutation confers drug resistance to FDA-approved targeted therapeutics imatinib mesylate, dasatinib, and nilotinib. We tested the ability of a recombinant yeast-based vaccine expressing the T315I-mutated BCR-ABL antigen to stimulate an anti-BCR-ABL^T315I immune response. The yeast-based immunotherapy significantly reduced or eliminated BCR-ABL^T315I leukemia cells from the peripheral blood of immunized animals and extended leukemia-free survival in a murine model of BCR-ABL⁺ leukemia compared to animals receiving sham injection or yeast expressing ovalbumin. With immunization, leukemic cells harboring BCR-ABL^T315I were selectively eliminated after challenge with a mixed population of BCR-ABL and BCR-ABL^T315I leukemias. In summary, yeast-based immunotherapy represents a novel approach against the emergence of cancer drug resistance by the pre-emptive targeted ablation of tumor escape mutants.