A phase I/II minor histocompatibility antigen-loaded dendritic cell vaccination trial to safely improve the efficacy of donor lymphocyte infusions in myeloma

L. E. Franssen*, M. W.H. Roeven, W. Hobo, R. Doorn, R. Oostvogels, J. H.F. Falkenburg, N. W. Van De Donk, M. G.D. Kester, H. Fredrix, K. Westinga, I. Slaper-Cortenbach, E. Spierings, M. J. Kersten, H. Dolstra, T. Mutis, N. Schaap, H. M. Lokhorst

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Allogeneic stem cell transplantation (allo-SCT) with or without donor lymphocyte infusions (DLI) is the only curative option for several hematological malignancies. Unfortunately, allo-SCT is often associated with GvHD, and patients often relapse. We therefore aim to improve the graft-versus-tumor effect, without increasing the risk of GvHD, by targeting hematopoietic lineage-restricted and tumor-associated minor histocompatibility antigens using peptide-loaded dendritic cell (DC) vaccinations. In the present multicenter study, we report the feasibility, safety and efficacy of this concept. We treated nine multiple myeloma patients with persistent or relapsed disease after allo-SCT and a previous DLI, with donor monocyte-derived mHag-peptide-loaded DC vaccinations combined with a second DLI. Vaccinations were well tolerated and no occurrence of GvHD was observed. In five out of nine patients, we were able to show the induction of mHag-specific CD8 + T cells in peripheral blood. Five out of nine patients, of which four developed mHag-specific T cells, showed stable disease (SD) for 3.5-10 months. This study shows that mHag-based donor monocyte-derived DC vaccination combined with DLI is safe, feasible and capable of inducing objective mHag-specific T-cell responses. Future research should focus on further improvement of the vaccination strategy, toward translating the observed T-cell responses into robust clinical responses.

Original languageEnglish
Pages (from-to)1378-1383
Number of pages6
JournalBone Marrow Transplantation
Volume52
Issue number10
DOIs
Publication statusPublished - 1 Oct 2017

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