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- W2777528125 abstract "2882 Background: We have previously developed and characterized 9mer peptide vaccines derived from carbonic anhydrase 9 (CA9), a tumor-associated antigen frequently expressed in renal cell carcinomas. To assess the safety and toxicity of the peptide vaccines (CA9p219, p288, p323), a phase-I clinical trial was carried out for patients with cytokine-refractory metastatic renal cell carcinoma. Methods: Twenty-three patients positive for human leukocyte antigen (HLA)-A24 with histologically confirmed renal cell carcinoma were enrolled in this study. Eligibility required progressive disease after standard cytokine therapy with interleukin-2 and/or interferon-alpha. Four weeks after any of prior anti-tumor therapy, patients were vaccinated subcutaneously with each peptide vaccine emulsified with incomplete Freund adjuvant at two weeks intervals. Before the first vaccination and after every three vaccinations, blood samples were taken from the patients for toxicity assessment and immunological study to evaluate the presence of cytotoxic T lymphocytes (CTLs) reactive to each peptide as well as CA9 expressing cancer cells. Clinical responses were investigated every three months. Results: Overall peptide vaccinations were generally tolerated with no major adverse events. The most frequent toxicity was skin redness and swelling at the vaccination site. Most of the patients developed peptide-specific CTLs and antibodies (IgG) after the 6th or 9th vaccination, and serial increase of peptide-specific CTL responses and peptide-reactive serum IgG production was observed thereafter. 51Cr release assay revealed that CA9 peptide vaccinations could induce direct killing against endogenously CA9 expressing cancer cells with HLA-A24 restricted manner. Peptide-specific DTH reactions were observed in six patients. Three patients with multiple lung metastases showed partial responses with disappearance and shrinking of metastatic lesions. Stable disease more than 6 months was observed in 6 patients for median duration of 12.2 months. Moreover, the median survival time was 26 months and progression free survival was 6.0 months. Conclusions: These results suggest that HLA-A24 restricted CA9 peptide vaccination therapy is safe and applicable for metastatic RCC patients." @default.
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- W2777528125 date "2006-04-15" @default.
- W2777528125 modified "2023-09-28" @default.
- W2777528125 title "Induction of specific anti-tumor responses by CA9 peptide vaccination in patients with metastatic renal cell carcinoma" @default.
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