Towards effective and safe immunotherapy after allogeneic stem cell transplantation: Identification of hematopoietic-specific minor histocompatibility antigen UTA2-1

R. Oostvogels, M. C. Minnema, M. Van Elk, R. M. Spaapen, G. D. Te Raa, B. Giovannone, A. Buijs, D. Van Baarle, A. P. Kater, M. Griffioen, E. Spierings, H. M. Lokhorst, T. Mutis

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Donor T cells directed at hematopoietic system-specific minor histocompatibility antigens (mHags) are considered important cellular tools to induce therapeutic graft-versus-tumor (GvT) effects with low risk of graft-versus-host disease after allogeneic stem cell transplantation. To enable the clinical evaluation of the concept of mHag-based immunotherapy and subsequent broad implementation, the identification of more hematopoietic mHags with broad applicability is imperative. Here we describe novel mHag UTA2-1 with ideal characteristics for this purpose. We identified this antigen using genome-wide zygosity-genotype correlation analysis of a mHag-specific CD8 + cytotoxic T lymphocyte (CTL) clone derived from a multiple myeloma patient who achieved a long-lasting complete remission after donor lymphocyte infusion from an human leukocyte antigen (HLA)-matched sibling. UTA2-1 is a polymorphic peptide presented by the common HLA molecule HLA-A*02:01, which is encoded by the bi-allelic hematopoietic-specific gene C12orf35. Tetramer analyses demonstrated an expansion of UTA2-1-directed T cells in patient blood samples after several donor T-cell infusions that mediated clinical GvT responses. More importantly, UTA2-1-specific CTL effectively lysed mHag + hematopoietic cells, including patient myeloma cells, without affecting non-hematopoietic cells. Thus, with the capacity to induce relevant immunotherapeutic CTLs, it's HLA-A*02 restriction and equally balanced phenotype frequency, UTA2-1 is a highly valuable mHag to facilitate clinical application of mHag-based immunotherapy.

Original languageEnglish
Pages (from-to)642-649
Number of pages8
Issue number3
Publication statusPublished - 1 Mar 2013


  • graft versus tumor
  • hematological malignancy
  • immunotherapy
  • minor histocompatibility antigens

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