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Long-term clinical and immunological effects of p53-SLP (R) vaccine in patients with ovarian cancer

  作者 Leffers, N; Vermeij, R; Hoogeboom, BN; Schulze, UR; Wolf, R; Hamming, IE; van der Zee, AG; Melief, KJ; van der Burg, SH; Daemen, T; Nijman, HW  
  选自 期刊  International Journal of Cancer;  卷期  2012年130-1;  页码  105-112  
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[摘要]Vaccine-induced p53-specific immune responses were previously reported to be associated with improved response to secondary chemotherapy in patients with small cell lung cancer. We investigated long-term clinical and immunological effects of the p53-synthetic long peptide (p53-SLP (R)) vaccine in patients with recurrent ovarian cancer. Twenty patients were immunized with the p53-SLP (R) vaccine between July 2006 and August 2007. Follow-up information on patients was obtained. Clinical responses to secondary chemotherapy after p53-SLP (R) immunizations were determined by computerized tomography and/or tumor marker levels (CA125). Disease-specific survival was compared to a matched historical control group. Immune responses were analyzed by flow cytometry, proliferation assay, interferon gamma (IFN-gamma) ELISPOT and/or cytokine bead array. Lymphocytes cultured from skin biopsy were analyzed by flow cytometry and proliferation assay. Of 20 patients treated with the p53-SLP (R) vaccine, 17 were subsequently treated with chemotherapy. Eight of these patients volunteered another blood sample. No differences in clinical response rates to secondary chemotherapy or disease-specific survival were observed between immunized patients and historical controls (p = 0.925, resp. p = 0.601). p53-specific proliferative responses were observed in 5/8 patients and IFN-gamma production in 2/7 patients. Lymphocytes cultured from a prior injection site showing inflammation during chemotherapy did not recognize p53-SLP (R). Thus, treatment with the p53-SLP (R) vaccine does not affect responses to secondary chemotherapy or survival, although p53-specific T-cells do survive chemotherapy.

 
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