Journal
JOURNAL OF CLINICAL ONCOLOGY
Volume 23, Issue 24, Pages 5779-5787Publisher
AMER SOC CLINICAL ONCOLOGY
DOI: 10.1200/JCO.2005.06.478
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Purpose Tumor-specific immunomonitoring is essential to evaluate the efficacy of vaccination against cancer. In this study, we investigated the predictive value of the presence or absence of antigen-specific T cells in biopsies from delayed-type hypersensitivity (DTH) sites. Patients and Methods In our ongoing clinical trials, HLA-A2.1 + melanoma patients were vaccinated with mature dendritic cells (DC) pulsed with melanoma-associated peptides (gp100 and tyrosinase) and keyhole limpet hemocyanin. Results After intradermal administration of a DTH challenge with gp100- and tyrosinase peptide-loaded DC, essentially all patients showed a positive induration. In clinically responding patients, T cells specific for the antigen preferentially accumulated in the DTH site, as visualized by in situ tetramer staining. Furthermore, significant numbers of functional gp100 and tyrosinase tetra mer-positive T cells could be isolated from these DTH biopsies, in accordance with the applied antigen in the DTH challenge. We observed a direct correlation between the presence of DC vaccine-related T cells in the DTH biopsies of stage IV melanoma patients and a positive clinical outcome (P = .0012). Conclusion These findings demonstrate the potency of this novel approach in the monitoring of vaccination studies in cancer patients.
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