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

Int J Cancer. 2012 Jan 1;130(1):105-12. doi: 10.1002/ijc.25980. Epub 2011 May 9.

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®) vaccine in patients with recurrent ovarian cancer. Twenty patients were immunized with the p53-SLP® vaccine between July 2006 and August 2007. Follow-up information on patients was obtained. Clinical responses to secondary chemotherapy after p53-SLP® 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-γ) 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® 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-γ production in 2/7 patients. Lymphocytes cultured from a prior injection site showing inflammation during chemotherapy did not recognize p53-SLP®. Thus, treatment with the p53-SLP® vaccine does not affect responses to secondary chemotherapy or survival, although p53-specific T-cells do survive chemotherapy.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Clear Cell / immunology
  • Adenocarcinoma, Clear Cell / metabolism
  • Adenocarcinoma, Clear Cell / therapy
  • Adenocarcinoma, Mucinous / immunology
  • Adenocarcinoma, Mucinous / metabolism
  • Adenocarcinoma, Mucinous / therapy
  • Antineoplastic Agents / therapeutic use
  • CA-125 Antigen / metabolism
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / therapeutic use*
  • Cell Proliferation
  • Cystadenocarcinoma, Serous / immunology
  • Cystadenocarcinoma, Serous / metabolism
  • Cystadenocarcinoma, Serous / therapy
  • Cytokines
  • Endometrial Neoplasms / immunology
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / therapy
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Humans
  • Immunization
  • Interferon-gamma
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / therapy*
  • Peptide Fragments / immunology*
  • Prospective Studies
  • T-Lymphocytes / immunology*
  • Tumor Suppressor Protein p53 / immunology*

Substances

  • Antineoplastic Agents
  • CA-125 Antigen
  • Cancer Vaccines
  • Cytokines
  • Peptide Fragments
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Interferon-gamma