title: Proteogenomic-based discovery of minor histocompatibility antigens with suitable features for immunotherapy of hematologic cancers.
abstract: Pre-clinical studies have shown that injection of allogeneic T cells primed against a single minor histocompatibility antigen (MiHA) could cure hematologic cancers (HC) without causing any toxicity to the host. However, translation of this approach in humans has been hampered by the paucity of molecularly defined human MiHAs. Using a novel proteogenomic approach, we have analyzed cells from 13 volunteers and discovered a vast repertoire of MiHAs presented by the most common HLA haplotype in European Americans: HLA-A*02:01;B*44:03. Notably, out of >6000 MiHAs, we have identified a set of 39 MiHAs that share optimal features for immunotherapy of HCs. These 'optimal MiHAs' are coded by common alleles of genes that are preferentially expressed in hematopoietic cells. Bioinformatic modeling based on MiHA allelic frequencies showed that the 39 optimal MiHAs would enable MiHA-targeted immunotherapy of practically all HLA-A*02:01;B*44:03 patients. Further extension of this strategy to a few additional HLA haplotypes would allow treatment of almost all patients.
authors: Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, Canada.|Department of Medicine, Université de Montréal, Montréal, QC, Canada.
authors: D P
authors: DP
authors: Granados
authors: Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, Canada.
authors: A
authors: A
authors: Rodenbrock
authors: Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, Canada.|Department of Informatics and Operational Research, Université de Montréal, Montréal, QC, Canada.
authors: J-P
authors: JP
authors: Laverdure
authors: Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, Canada.
authors: C
authors: C
authors: Côté
authors: Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, Canada.
authors: O
authors: O
authors: Caron-Lizotte
authors: Centre de recherche de l'Hôpital Maisonneuve-Rosemont, Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada.
authors: C
authors: C
authors: Carli
authors: Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, Canada.|Department of Medicine, Université de Montréal, Montréal, QC, Canada.
authors: H
authors: H
authors: Pearson
authors: Centre de recherche de l'Hôpital Maisonneuve-Rosemont, Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada.
authors: V
authors: V
authors: Janelle
authors: Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, Canada.
authors: C
authors: C
authors: Durette
authors: Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, Canada.
authors: E
authors: E
authors: Bonneil
authors: Department of Medicine, Université de Montréal, Montréal, QC, Canada.|Centre de recherche de l'Hôpital Maisonneuve-Rosemont, Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada.|Division of Hematology-Oncology, Hôpital Maisonneuve-Rosemont, Montreal, QC, Canada.
authors: D C
authors: DC
authors: Roy
authors: Department of Medicine, Université de Montréal, Montréal, QC, Canada.|Centre de recherche de l'Hôpital Maisonneuve-Rosemont, Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada.|Division of Hematology-Oncology, Hôpital Maisonneuve-Rosemont, Montreal, QC, Canada.
authors: J-S
authors: JS
authors: Delisle
authors: Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, Canada.|Department of Informatics and Operational Research, Université de Montréal, Montréal, QC, Canada.
authors: S
authors: S
authors: Lemieux
authors: Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, Canada.|Department of Chemistry, Université de Montréal, Montréal, QC, Canada.
authors: P
authors: P
authors: Thibault
authors: Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, Canada.|Department of Medicine, Université de Montréal, Montréal, QC, Canada.|Division of Hematology-Oncology, Hôpital Maisonneuve-Rosemont, Montreal, QC, Canada.
authors: C
authors: 0000-0001-9453-7383
authors: C
authors: Perreault
mesh_terms: D002478:Cells, Cultured; D005260:Female; D015789:HLA-A2 Antigen; D059948:HLA-B44 Antigen; D006239:Haplotypes; D019337:Hematologic Neoplasms / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D015778:Minor Histocompatibility Antigens / Q000627:therapeutic use*; D000071696:Proteogenomics / Q000379:methods*
chemical_list: C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D059948:HLA-B44 Antigen; D015778:Minor Histocompatibility Antigens