Abstract
Survivin is a member of the inhibitors of apoptosis family and is overexpressed in different types of malignancies. Cytotoxic T cells recognizing survivin epitopes can be elicited in vitro and by vaccination in patients with leukemia, breast cancer, and melanoma. We did this study to investigate whether survivin-specific CD8+ T cells occur in patients with multiple myeloma. An HLA-A2.1-binding survivin peptide was used to detect peptide-specific T cells by a quantitative real-time PCR to measure antigen-specific IFN-gamma mRNA expression in 23 patients with myeloma and 21 healthy volunteers. T cells producing IFN-gamma in response to survivin were further analyzed for expression of CD45RA and CCR7 to determine phenotypic characterization. Additional immunohistochemical analyses of survivin antigen expression in bone marrow specimens of patients was done. T cells recognizing HLA-A2.1-binding survivin peptide were detected in 9 of 23 patients and in 1 of 21 healthy volunteers. Survivin-reactive T cells were identified as terminally differentiated effector T cells (CD8+, CD45RA+, and CCR7-). Positive survivin expression of myeloma cells in bone marrow specimens was shown in 7 of 11 patients. We provide, for the first time, evidence of T cell reactivity against survivin antigen in patients with multiple myeloma. Our data suggest the immunogenicity of survivin antigen in multiple myeloma and that immunotherapeutic strategies using survivin as a target antigen might be an option for patients with this disease.
Highlights
Survivin is a member of the inhibitors of apoptosis family and is overexpressed in different types of malignancies
Survivin is a member of the inhibitor of apoptosis gene family that has recently been suggested as a promising target antigen in different malignancies [8, 9, 11, 42, 43]
Both spontaneous specific T-cell reactivity and antibody response to survivin have been recently detected in patients with leukemia, melanoma, breast, lung, and colorectal cancer (15 – 20)
Summary
Survivin is a member of the inhibitors of apoptosis family and is overexpressed in different types of malignancies. A member of the inhibitor of apoptosis gene family, has recently been suggested as a promising target antigen for immunotherapeutic approaches in different malignancies (8 – 11) and has not yet been examined in multiple myeloma. It is present during normal fetal development but is undetectable in most terminally differentiated adult tissues except thymus cells, CD34+ bone marrow – derived hematopoietic progenitor cells, basal colonic epithelial cells, and activated endothelial www.aacrjournals.org. Several survivin epitopes could be identified recently, capable of inducing specific cytotoxic T-cell responses in patients with leukemia, breast cancer, and melanoma (15 – 18). A clinical vaccination study using survivin peptide – pulsed dendritic cells has been recently done in melanoma and did not show major toxicities (e.g., autoimmune reaction) after immunization [21]
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