Vaccination with Dendritic Cell Myeloma Fusions in Conjunction with Stem Cell Transplantation and PD-1 Blockade.

摘要

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 characteristic of patients with malignancy. An important element contributing to tumor mediated immune suppression is the PD-1/PDL-1 pathway. PD-L1 exerts a significant role in promoting T cell tolerance by binding PD-1 on activated T cells and suppressing their capacity to secrete stimulatory cytokines. We have demonstrated that blockade of this pathway results in enhanced immune responses to DC/myeloma 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 with myeloma. These endpoints will then be assessed in patients undergoing combined therapy with the vaccine and antibody.