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Vaccination with Dendritic Cell Myeloma Fusions in Conjunction With Stem Cell Transplantation and PD1 Blockade
Final rept. 1 May 2009-30 Apr 2013
BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
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Most patients with multiple myeloma achieve a complete or near complete response following autologous transplantation. However, patients experience disease relapse from a persistent reservoir of chemotherapy resistant disease. There has been strong interest in developing immunotherapeutic strategies to eradicate residual disease following autologous transplantation. Our group has developed a tumor vaccine model whereby dendritic cells are fused with tumor cells. In clinical trials, vaccination with fusion cell results in anti-tumor immune and disease responses in a subset of patients. However, vaccine efficacy is blunted by tumor mediated immune suppression and the increased presence of regulatory T cells characteristpatients with malignancy. An important element contributing to tumor mediated immune suppression is the PD-1PDL-1 pathway. PD-L1 exerts a significant role in promoting T cell tolerance by binding PD-1 on activated T cells and suppressintheir capacity to secrete stimulatory cytokines. We have demonstrated that blockade of this pathway results in enhanced immune responses to DCmyeloma fusion cells ex vivo. In the proposed study, we will examine toxicity, immunologic effect and clinical efficacy of CT-011 therapy following stem cell transplantation for patients witih myeloma. These endpoints will then be assessed in patients undergoing combined therapy with the vaccine and antibody.
APPROVED FOR PUBLIC RELEASE