Allogeneic stem cell transplantation (alloSCT) followed by donor lymphocyte infusion (DLI) can be applied as immunotherapeutic intervention to treat malignant diseases.
Here, we describe a patient with progressive metastatic clear cell renal cell carcinoma (RCC) who was treated with T cell depleted non-myeloablative alloSCT and DLI resulting in disease regression accompanied by extensive graft versus host disease (GVHD). We characterized the specificity of this immune response, and detected a dominant T cell population recognizing a novel minor histocompatibility antigen (MiHA) designated LB-FUCA2-1V. T cells specific for LB-FUCA2-1V were shown to recognize RCC cell lines, supporting a dominant role in the graft versus tumor (GVT) reaction. However, coinciding with the gradual disappearance of chronic GVHD, the anti-tumor effect declined and 3 years after alloSCT the metastases became progressive again. To re-initiate the GVT reaction, escalating doses of DLI were given, but no immune response could be induced and the patient died of progressive disease 8.5 years after alloSCT. Gene expression studies illustrated that only a minimal number of genes shared expression between RCC and professional antigen presenting cells but were not expressed by non-malignant healthy tissues, indicating that in patients suffering from RCC, GVT reactivity after alloSCT may be unavoidably linked to GVHD.
Written by:
van Bergen CA, Verdegaal EM, Honders MW, Hoogstraten C, Steijn-van Tol AQ, de Quartel L, de Jong J, Meyering M, Falkenburg JH, Griffioen M, Osanto S. Are you the author?
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands; Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
Reference: PLoS One. 2014 Jan 15;9(1):e85198.
doi: 10.1371/journal.pone.0085198
PubMed Abstract
PMID: 24454818
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