PMID- 16037388 OWN - NLM STAT- MEDLINE DCOM- 20051215 LR - 20220310 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 106 IP - 10 DP - 2005 Nov 15 TI - Induction of HM1.24 peptide-specific cytotoxic T lymphocytes by using peripheral-blood stem-cell harvests in patients with multiple myeloma. PG - 3538-45 AB - HM1.24 antigen is preferentially overexpressed in multiple myeloma (MM) cells but not in normal cells. To explore the potential of HM1.24 as a target for cellular immunotherapy, we selected 4 HM1.24-derived peptides that possess binding motifs for HLA-A2 or HLA-A24 by using 2 computer-based algorithms. The ability of these peptides to generate cytotoxic T lymphocytes (CTLs) was examined in 20 healthy donors and 6 patients with MM by a reverse immunologic approach. Dendritic cells (DCs) were induced from peripheral-blood mononuclear cells of healthy donors or peripheral-blood stem-cell (PBSC) harvests from patients with MM, and autologous CD8(+) T cells were stimulated with HM1.24 peptide-pulsed DCs. Both interferon-gamma-producing and cytotoxic responses were observed after stimulation with either HM1.24-126 or HM1.24-165 peptides in HLA-A2 or HLA-A24 individuals. The peptide-specific recognition of these CTLs was further confirmed by tetramer assay and cold target inhibition assay. Importantly, HM1.24-specific CTLs were also induced from PBSC harvests from patients with MM and these CTLs were able to kill MM cells in an HLA-restricted manner. These results indicate the existence of functional DCs and HM1.24-specific CTL precursors within PBSC harvests and provide the basis for cellular immunotherapy in combination with autologous PBSC transplantation in MM. FAU - Jalili, Ali AU - Jalili A AD - Department of Medicine and Bioregulatory Sciences, Institute of Health Biosciences, University of Tokushima Graduate School, Japan. FAU - Ozaki, Shuji AU - Ozaki S FAU - Hara, Tomoko AU - Hara T FAU - Shibata, Hironobu AU - Shibata H FAU - Hashimoto, Toshihiro AU - Hashimoto T FAU - Abe, Masahiro AU - Abe M FAU - Nishioka, Yasuhiko AU - Nishioka Y FAU - Matsumoto, Toshio AU - Matsumoto T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20050721 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Antigens, CD) RN - 0 (BST2 protein, human) RN - 0 (GPI-Linked Proteins) RN - 0 (HLA-A Antigens) RN - 0 (HLA-A2 Antigen) RN - 0 (HLA-A24 Antigen) RN - 0 (Membrane Glycoproteins) RN - 0 (Peptides) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Antigens, CD MH - Cell Line, Tumor MH - Dendritic Cells/cytology/*immunology MH - Female MH - GPI-Linked Proteins MH - HLA-A Antigens/immunology MH - HLA-A2 Antigen/immunology MH - HLA-A24 Antigen MH - Hematopoietic Stem Cells/cytology/*immunology MH - Humans MH - Interferon-gamma/immunology MH - Male MH - Membrane Glycoproteins/*immunology/pharmacology MH - Multiple Myeloma/*immunology/therapy MH - Peptides/*immunology/pharmacology MH - Peripheral Blood Stem Cell Transplantation/methods MH - T-Lymphocytes, Cytotoxic/*immunology MH - Transplantation, Homologous EDAT- 2005/07/23 09:00 MHDA- 2005/12/16 09:00 CRDT- 2005/07/23 09:00 PHST- 2005/07/23 09:00 [pubmed] PHST- 2005/12/16 09:00 [medline] PHST- 2005/07/23 09:00 [entrez] AID - S0006-4971(20)68499-3 [pii] AID - 10.1182/blood-2005-04-1438 [doi] PST - ppublish SO - Blood. 2005 Nov 15;106(10):3538-45. doi: 10.1182/blood-2005-04-1438. Epub 2005 Jul 21.