title: Long-term clinical and immunological effects of p53-SLP® vaccine in patients with ovarian cancer.
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.
authors.affiliation: Department of Gynecologic Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Ninke
authors.initials: N
authors.lastname: Leffers
authors.forename: Renee
authors.initials: R
authors.lastname: Vermeij
authors.forename: Baukje-Nynke
authors.initials: BN
authors.lastname: Hoogeboom
authors.forename: Ute R
authors.initials: UR
authors.lastname: Schulze
authors.forename: Rinze
authors.initials: R
authors.lastname: Wolf
authors.forename: Ineke E
authors.initials: IE
authors.lastname: Hamming
authors.forename: Ate G
authors.initials: AG
authors.lastname: van der Zee
authors.forename: Kees J
authors.initials: KJ
authors.lastname: Melief
authors.forename: Sjoerd H
authors.initials: SH
authors.lastname: van der Burg
authors.forename: Toos
authors.initials: T
authors.lastname: Daemen
authors.forename: Hans W
authors.initials: HW
authors.lastname: Nijman
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D002288:Adenocarcinoma, Mucinous / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018394:CA-125 Antigen / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use*; D049109:Cell Proliferation; D018284:Cystadenocarcinoma, Serous / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D016207:Cytokines; D016889:Endometrial Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D010446:Peptide Fragments / Q000276:immunology*; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000276:immunology*; D016159:Tumor Suppressor Protein p53 / Q000276:immunology*
chemical_list: D000970:Antineoplastic Agents; D018394:CA-125 Antigen; D019496:Cancer Vaccines; D016207:Cytokines; D010446:Peptide Fragments; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D007371:Interferon-gamma