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 p rotein, is aberrantly expressed on the tumor cells in patients with multipl e 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 us ed Sp17 protein-pulsed dendritic cells to generate HLA class I-restricted S p17-specific CTL from a previously unimmunized healthy donor. These CTL wer e able to lyse autologous Epstein-Barr virus-transformed lymphoblastoid cel ls in a Sp17-dependent manner. Target lysis was HLA-Al and HLA-B27 restrict ed. Cytotoxicity could be blocked by antibodies against monomorphic HLA cla ss I, HLA-A1 and HLA-B27 molecules but not HLA class II molecules. Most imp ortantly, the CTL lysed HLA class I-matched Sp17-positive tumor cells, sugg esting that Sp17 is processed and presented in association with the HLA cla ss I molecules in Sp17-positive tumor cells in a concentration and configur ation 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 sug gest the potential for the generation and administration of donor-derived S p17-specific CTL to augment GVM without inducing GVHD following allogeneic stem cell transplant for MM.