Tissue biopsies of last vaccination site prior to first vaccinationtumor biopsy
Tissue biopsies of the last vaccination site and of the VIN lesion prior to the first vaccination and 3 months after the last vaccination were analysed for the presence of HPV16-specific T cells.
The IFN?-ELISPOT analysis and proliferation with its accompanying cytokine production revealed a strong and broad vaccine-induced T cell response. The strength of the immune response (defined as breath and magnitude of the response) was significantly higher in the patients with a complete remission (CR) than in the patients with no changes (NC) in the lesion size. Phenotypical anlaysis revealed a strong induction of CD4+ T-cells specifically against HPV16 E6 and E7, whereas CD8+ T cells were found merely against HPV16 E6 and to a less broad array of epitopes within each patient. This analysis was done after one in vitro restimulation, however, by directly ex vivo flow cytometric analysis hardly any CD8+ T cell response could be detected. The T cell cultures obtained from the biopsies taken of the last vaccination site were found to be HPV16 peptides specific in 3/5 tested NR patients and in 4/5 tested CR. However, recognition of the recombinant HPV16 E6 and/or E7 protein was observed in 1/5 cultures from NR patients and 4/5 cultures of the CR patients, suggesting the differences in vaccine-induced T-cell reactivity. Tissue biopsies of the VIN lesion before and after vaccination showed only in one patient a HPV16-specific T-cell response, which was against HPV16 E6 and merely of the type 2 cytokine producing T cells. Notably, no T-cell cultures could be obtained from VIN biopsies taken from the CR patients. In conclusion, the HPV16 E6 and E7 synthetic long peptides vaccine is highly immunogenic, in that it increases the number and activity of HPV16-specific CD4+ and CD8+ T-cells to a broad array of epitopes in all patients. The expansion of CD4+ and CD8+ tumor-specific T-cells, both considered to be important in the anti-tumor response indicates the immunotherapeutic potential of this vaccine. Addition of a strong toll-like receptor ligand might increase the CD8 response in frequency and to a broader set of epitopes.
- organism type
- Homo sapiens