A novel multi-epitope vaccine from MMSA-1 and DKK1 for multiple myeloma immunotherapy

British Journal of Haematology
Chenyang LuFuling Zhou

Abstract

The identification of novel tumour-associated antigens is urgently needed to improve the efficacy of immunotherapy for multiple myeloma (MM). In this study, we identified a membrane protein MMSA-1 (multiple myeloma special antigen-1) that was specifically expressed in MM and exhibited significantly positive correlation with MM. We then identified HLA-A*0201-restricted MMSA-1 epitopes and tested their cytotoxic T lymphocyte (CTL) response. The MMSA-1 epitope SLSLLTIYV vaccine was shown to induce an obvious CTL response in vitro. To improve the immunotherapy, we constructed a multi-epitope peptide vaccine by combining epitopes derived from MMSA-1 and Dickkopf-1 (DKK1). The effector T cells induced by multi-epitope peptide vaccine-loaded dendritic cells lysed U266 cells more effectively than MMSA-1/DKK1 single-epitope vaccine. In myeloma-bearing severe combined immunodeficient mice, the multi-epitope vaccine improved the survival rate significantly compared with single-epitope vaccine. Consistently, multi-epitope vaccine decreased the tumour volume greatly and alleviated bone destruction. The frequencies of CD4+ and CD8+ T cells was significantly increased in mouse blood induced by the multi-epitope vaccine, indicating that it inh...Continue Reading

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Citations

Jun 2, 2018·Expert Review of Hematology·Jessica LiegelJacalyn Rosenblatt
Sep 12, 2017·Cellular & Molecular Immunology·Lifang Zhang
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