Vaccination with dendritic cell/tumor fusion cells results in cellular and humoral antitumor immune responses in patients with multiple myeloma

Abstract

We have developed a tumor vaccine in which patient-derived myeloma cells are chemically fused with autologous dendritic cells (DCs) such that a broad spectrum of myeloma-associated antigens are presented in the context of DC-mediated costimulation. We have completed a phase 1 study in which patients with multiple myeloma underwent serial vaccination with the DC/multiple myeloma fusions in conjunction with granulocytemacrophage colony-stimulating factor. DCs were generated from adherent mononuclear cells cultured with granulocyte-

Augmenting Autologous Stem Cell Transplantation to Improve Outcomes in Myeloma

“…1). A phase I trial of autologous DC-myeloma cell fusion cells injected into myeloma patients found these induced expansion of myeloma-specific T cells in vivo, and stabilised disease progression in 11 of 16 patients (Rosenblatt et al, 2011). A small trial from the Mayo clinic of ex vivo stimulated DCs accompanying ASCT found improved survival compared to matched historical controls (Lacy et al, 2009), and a small Czech study looking at ex vivo stimulated DCs as monotherapy in pretreated patients found a modest improvement in outcomes (Zahradova et al, 2012).…”

Allogeneic stem cell transplantation for multiple myeloma: is there a future?

“…68 It has also been demonstrated that LEN by promoting T-cell proliferation augments response to a myeloma-specific tumor vaccine. 69,70 These studies suggested that in the post allotransplant setting, LEN may induce disease response and also GVHD. Objective responses to salvage treatment with LEN were noted in 83% of patients (including 29% CR) relapsing after an allotransplant.…”

“…Based on the extensive preclinical evidence of PD1 expression on T cells from MM, 83 numerous phase I/II dose escalation study using the anti-PD1 agent in MM is being conducted. 54 In one phase II clinical trial, Rosenblatt et al 70 demonstrate that repeated immunization with a DC-tumor fusion vaccine after ASCT induces myeloma-specific immunity and improves clinical response. 70 Recent study with the immunostimulatory monoclonal Ab elotuzumab in combination with LEN and dexamethasone has shown promising results with 1-year PFS of 68% vs 57% at 1 year (P ⩽ 0.001).…”

“…54 In one phase II clinical trial, Rosenblatt et al 70 demonstrate that repeated immunization with a DC-tumor fusion vaccine after ASCT induces myeloma-specific immunity and improves clinical response. 70 Recent study with the immunostimulatory monoclonal Ab elotuzumab in combination with LEN and dexamethasone has shown promising results with 1-year PFS of 68% vs 57% at 1 year (P ⩽ 0.001). 7 Early pilot studies have shown promising signs of efficacy with the CAR T cells in MM.…”

New Insights into Therapeutic Targets in Myeloma

“…For example, vaccination with fusions of dendritic cells with tumor cells allows for the generation of T celland humoral tumor-specific host immunity in preclinical models of murine 53 and human MM. 54 Derived clinical trials of MM-DC fusion vaccinations are achieving high rates of complete response posttransplantation. An alternative promising strategy is the use of peptides for vaccination.…”