Sperm protein 17 (Sp17) in multiple myeloma: opportunity for myeloma-specific donor T cell infusion to enhance graft-versus-myeloma effect without increasing graft-versus-host disease risk.
We recently found that sperm protein 17 (Sp17), a spermatozoa-restricted protein, is aberrantly expressed on the tumor cells in patients with multiple myeloma (MM). It may therefore be possible to generate donor-derived Sp17-specific CTL for administration following allogeneic stem cell transplant to augment graft-versus-myeloma (GVM) effect without inducing a global GVHD. To assess this approach, we have produced recombinant Sp17 protein and used Sp17 protein-pulsed dendritic cells to generate HLA class I-restricted Sp17-specific CTL from a previously unimmunized healthy donor. These CTL were able to lyse autologous Epstein-Barr virus-transformed lymphoblastoid cells in a Sp17-dependent manner. Target lysis was HLA-A1 and HLA-B27 restricted. Cytotoxicity could be blocked by antibodies against monomorphic HLA class I, HLA-A1 and HLA-B27 molecules but not HLA class II molecules. Most importantly, the CTL lysed HLA class I-matched Sp17-positive tumor cells, suggesting that Sp17 is processed and presented in association with the HLA class I molecules in Sp17-positive tumor cells in a concentration and configuration that could be recognized by recombinant protein-primed CTL. Analysis by flow cytometry of the CTL indicated that they were predominantly CD8 in phenotype and they produced IFN-gamma and very little IL-4. Our results suggest the potential for the generation and administration of donor-derived Sp17-specific CTL to augment GVM without inducing GVHD following allogeneic stem cell transplant for MM.
Chiriva-Internati
M
M
Center for Immunology and Microbial Disease and Department of Medicine, Albany Medical College, Albany, NY 12208, USA.
Wang
Z
Z
Xue
Y
Y
Bumm
K
K
Hahn
A B
AB
Lim
S H
SH
D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D000954:Antigens, Surface; D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D004198:Disease Susceptibility / Q000276:immunology; D004926:Escherichia coli / Q000235:genetics; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008565:Membrane Proteins; D009101:Multiple Myeloma / Q000276:immunology* / Q000628:therapy*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D013379:Substrate Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000637:transplantation*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D011994:Recombinant Proteins; C090172:SPA17 protein, human