Treatment of Post-Transplanted, Relapsed Patients with Hematological Malignancies by Infusion of HLA-Matched, Allogeneic-Dendritic Cells (DCs) Pulsed with Irradiated Tumor Cells and Primed T Cells

Abstract

Patients with hematological malignancies who relapse after bone marrow transplantation (BMT) are often treated with donor lymphocyte infusion. However, this procedure often results in graft-versus-host disease (GVHD). While, Dendritic cells (DCs), which present antigens to naive T cells, have been used in the immunotherapy of cancer, this approach has been logistically difficult due to limiting numbers of DCs. We have now developed a method for obtaining a large number of DCs by treating the granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSCs) from healthy donors with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4), and tumor necrosis factor-alpha (TNF-alpha). The resulting cells possess the morphologic, phenotypic, and functional characteristics of mature DCs. In in vitro studies, culture of these HLA-matched donor derived-DCs with irradiated each patient's tumor cells as an antigen source, followed by incubation with T cells from the patient, induced the production of highly cytotoxic T lymphocytes (CTLs) specific for the respective tumor cells in the semi-allogeneic setting. A transient, but objective clinical response was obtained in the absence of GVHD when we injected the DCs which had been pulsed with irradiated tumor cells as well as primed T cells from the same original donor of related- allogeneic stem cell transplantation into the relapsed patients. Our findings suggest that treatment of relapsed patients with such donor-derived DCs, and primed T cells may be effective as an adjunctive immunotherapy.

Safety and tolerability of allogeneic dendritic cell vaccination with induction of Wilms tumor 1–specific T cells in a pediatric donor and pediatric patient with relapsed leukemia: a case report and review of the literature

“…A literature review identified six patients with hematological malignancies who received donor-derived allogeneic DC vaccines after HSCT, including this present case (Table I). It is noteworthy that none of them had GVHD or systemic adverse events after allogeneic DC vaccination pulsed with tumor lysate [7] or WT1 peptide [8]. Together, previous and current reports suggest that leukemia antigenespecific allogeneic DC vaccination should be safe and well-tolerated by post-transplant relapsed patients, even in pediatric patients who received allografts from their sibling donors.…”

Potential of dendritic cell immunotherapy for relapse after allogeneic hematopoietic stem cell transplantation, shown by WT1 peptide‐ and keyhole limpet hemocyanin‐pulsed, donor‐derived dendritic cell vaccine for acute myeloid leukemia

“…There have been two reports on DC vaccination after allo-SCT in humans. In the first report, four patients were vaccinated with donor-derived DCs pulsed with autologous tumor cells for relapse of leukemia or lymphoma [15]. The injected cell populations contained substantial numbers ( 40%) of T cells primed in vitro.…”

Induction of multiple myeloma-reactive T cells during post-transplantation immunotherapy with donor lymphocytes and recipient DCs

“…This approach circumvents the obstacle of cryopreservation and has previously proved to be safe as post-transplantation therapy. 20,21,22 In conclusion, this case report describes an interesting mHAspecific T-cell response in a MM patient who was successfully treated with partial T-cell-depleted RIC --SCT followed by DLI and DC vaccination. During post-transplantation immunotherapy, measurable M-protein disappeared in the patient resulting in long-term CR.…”