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

Ninke Leffers, Renee Vermeij, Baukje-Nynke Hoogeboom, Ute R. Schulze, Rinze Wolf, Ineke E. Hamming, Ate G. van der Zee, Kees J. Melief, Sjoerd H. van der Burg, Toos Daemen, Hans W. Nijman*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

49 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)105-112
Number of pages8
JournalInternational Journal of Cancer
Volume130
Issue number1
DOIs
Publication statusPublished - 1-Jan-2012

Keywords

  • p53
  • immunotherapy
  • survival
  • ovarian cancer
  • ADVANCED BREAST-CANCER
  • P53-SPECIFIC IMMUNE-RESPONSES
  • CELL LUNG-CANCER
  • DENDRITIC CELLS
  • INDUCTION
  • TUMORS

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