Abstract
Survivin is a member of the inhibitors of apoptosis family and is expressed in different types of malignancies including multiple myeloma. Cytotoxic T cells recognizing survivin epitopes can be elicited in vitro and by vaccination in human individuals. We performed this study to investigate whether survivin peptide specific CD8 T cells occur in patients with multiple myeloma (MM) and in healthy individuals. To detect antigen specific T-cells, we incubated PBMC from HLA-A2.1 positive patients and healthy individuals with antigen-presenting-cells (C1R-A2) pulsed or not pulsed with a recently described, HLA-A2.1 binding survivin derived peptide (Survpep). We used quantitative real time PCR to measure IFN-gamma mRNA expression for the detection of peptide specific CTL in 23 patients and 21 healthy individuals. A peptide stimulation index (SI, test peptide reactivity / no peptide reactivity) of 2.0 or greater was considered a positive response. CD8 T cells recognizing Survpep could be detected in vitro in 9/23 (39%) patients with MM (SI ranging from 2.9 to 83) and 1/21 (5%) healthy individuals (SI 7). Positive responses were confirmed by 4-colour flow cytometry for intracellular IFN-gamma production. T cells producing IFN-gamma were further analyzed for expression of CD45RA and CCR7 to determine phenotypic characteristics in two patients (SI 83 and 63) identifying them as terminally differentiated effector T cells (CD8+, CD45RA+, CCR7−). Additionally, positive expression of survivin antigen in tumor cells was confirmed by imminohistochemical analysis of patients bone marrow specimen. In conclusion we provide for the first time evidence for T cell reactivity against Survivin antigen in patients with MM. Our data suggest (1) the immunogenicity of survivin antigen in multiple myeloma and (2) that survivin may be a useful candidate antigen for cellular immunotherapy of multiple myeloma.
CD8 T cell response (SI) to Survivin Peptide in patients with multiple myeloma (MM, n=23) and healthy individuals (HI, n=21)
CD8 T cell response (SI) to Survivin Peptide in patients with multiple myeloma (MM, n=23) and healthy individuals (HI, n=21)
