Successful Generation of Sperm Protein 17 (Sp17)‐Specific Cytotoxic T Lymphocytes from Normal Donors: Implication for Tumour‐Specific Adoptive Immunotherapy Following Allogeneic Stem Cell Transplantation for Sp17‐Positive Multiple Myeloma

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Abstract
Sperm protein 17 (Sp17) is a highly immunogenic cancer‐testis antigen expressed by tumour cells from up to 30% of patients with multiple myeloma (MM). We recently successfully generated Sp17‐specific human leucocyte antigen (HLA)‐A1 and B27‐restricted cytotoxic T lymphocytes (CTLs) from the peripheral blood of a healthy donor. Because CTLs were able to kill HLA‐matched fresh myeloma cells, it may be possible to generate and administer myeloma‐specific donor T cells to MM patients following allogeneic stem cell transplantation to enhance graft‐versus‐myeloma (GVM) without inducing graft‐versus‐host disease (GVHD). To determine how widely applicable this approach is, we have determined the ability to generate Sp17‐specific CTLs from four consecutive healthy donors with other HLA class I phenotypes. We found that Sp17‐specific HLA class I‐restricted CTLs could be easily generated from all four donors. Sp17‐specific CTLs were primarily CD8 in phenotype and produced interferon‐γ and very little interleukin‐4. These T cells killed target cells primarily via the perforin‐mediated route. These results therefore suggest that myeloma‐specific donor T‐cell infusion that targets Sp17 to selectively enhance GVM could be applicable to patients with Sp17+ MM.