Expression of minor histocompatibility antigen, HA-1, in solid tumor cells

Abstract

HA-1 expression in the mRNA level is higher in cells of hematopoietic origin, but this tissue distribution is not strictly restricted. Some solid tumor cells and tissues express HA-1 gene equal to hematopoietic cells.

Aberrant expression of the hematopoietic-restricted minor histocompatibility antigen LRH-1 on solid tumors results in efficient cytotoxic T cell-mediated lysis

“…Here, we analyzed the expression of the LRH-1-encoding P2X5 gene in a large panel of solid tumor cell lines and primary tumor specimens using real-time quantitative RT-PCR. SigniWcant P2X5 mRNA levels were detected in 31% of the solid tumor cell lines tested, including RCC, melanoma, colorectal carcinoma, [12,16], ECGF-1 [23], and BCL2A1 [2,24]. Enlargement of the panel of MiHA is essential for development of eVective post-transplantation immunotherapy.…”

“…The following solid tumor cell lines were used: RCC cell lines SKRC 1,7,10,12,17,18,24,33,35,52,and 59 were kindly provided by Dr. E. Oosterwijk (Department of Urology, Radboud University Nijmegen Medical Centre (RUNMC), Nijmegen, The Netherlands); melanoma cell lines BLM, FM3, MEL397, and 518A2 were kindly provided by Dr. J. de Vries (Department of Tumor Immunology, RUNMC, Nijmegen, The Netherlands); colorectal carcinoma cell lines HT29, KATO3, HCT15, HCT116, RKO, SW480, and SW620, and brain cancer cell lines BE(-2)C, CHP212, DAOY, D283med, PFSK-1, SK-N-DZ, SK-N-SH, SW1088, TE671, and U-87MG, and breast cancer cell lines BT549, CAMA-1, MCF-7, MDA-MB-134VI, MDA-MB-157, MDA-MB-175VII, MDA-MB-361, MDA-MB-436, SK-BR-3, and T47D were kindly provided by Dr. M. Schutte (Department of Medical Oncology, Josephine Nefkens Institute, Erasmus University Medical Center, Rotterdam, The Netherlands). Skin-derived Wbroblasts were kindly provided by S. van der Velde-Visser (Department of Human Genetics, RUNMC, Nijmegen, The Netherlands).…”

Steric Hindrance and Fast Dissociation Explain the Lack of Immunogenicity of the Minor Histocompatibility HA-1Arg Null Allele

“…Therefore, these two minor histocompatibility Ag types have discriminative roles in graft-versus-host disease and graft-versus-tumor reactivity: the broad minor histocompatibility peptides are involved in both disorders, whereas the restricted peptides are crucial for the graft-versus-tumor responses. The HA-1 minor histocompatibility Ag is hematopoietic system specific but shows additional expression on epithelial cancer cells while absent on the normal epithelial cell counterpart (4,5). Consequently, this minor histocompatibility Ag can be applied as an immunotherapeutic tool in SCT such as in cellular adoptive immunotherapy with HA-1-specific CTLs or in boosting the graft-versus-tumor responses with HA-1 peptide (6).…”

Hypomethylating drugs convert HA-1–negative solid tumors into targets for stem cell–based immunotherapy

“…7 Thus, cancer-specific mHags provide the unique option to boost the GVT effect without inducing severe GVHD. The hematopoiesisrestricted mHag HA-1 is aberrantly expressed in most solid tumors, 8,9 allowing cancer cell killing by HA-1-specific cytotoxic T lymphocytes (HA-1 CTLs) in vitro. 8,10 The power of HA-1 as an immunotherapeutic target on cancer cells in vivo has recently been shown by the eradication of human cancer metastases by HA-1 CTLs in immunodeficient mice.…”

“…14 The expression of HA-1 mRNA in 60% to 70% of cancer cell lines and primary tumors of most entities already indicates a broad applicability of HA-1 as an immunotherapeutic target on solid tumors. 8,9 Induction of HA-1 gene expression in the remaining estimated 30% to 40% of HA-1 neg cancers may further extend the usability of HA-1 as an immunotherapeutic tool. However, the mechanisms of transcriptional regulation of HA-1 in solid tumors, which may provide drug targets for HA-1 induction in HA-1 neg cancers, are as yet unknown.…”