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Immunization with a P53 synthetic long peptide vaccine induces P53‐specific immune responses in ovarian cancer patients, a phase II trial
Author(s) -
Leffers Ninke,
Lambeck Annechien J.A.,
Gooden Marloes J.M.,
Hoogeboom BaukjeNynke,
Wolf Rinze,
Hamming Ineke E.,
Hepkema Bouke G.,
Willemse Pax H.B.,
Molmans Barbara H.W.,
Hollema Harry,
Drijfhout Jan W.,
Sluiter Willem J.,
Valentijn A. Rob P.M.,
Fathers Loraine M.,
Oostendorp Jaap,
van der Zee Ate G.J.,
Melief Cornelis J.,
van der Burg Sjoerd H.,
Daemen Toos,
Nijman Hans W.
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24597
Subject(s) - elispot , medicine , immunogenicity , tolerability , immunotherapy , peptide vaccine , immunology , immune system , ovarian cancer , clinical trial , toxicity , oncology , cancer , t cell , antibody , epitope , adverse effect
The prognosis of ovarian cancer, the primary cause of death from gynecological malignancies, has only modestly improved over the last decades. Immunotherapy is one of the new treatment modalities explored for this disease. To investigate safety, tolerability, immunogenicity and obtain an impression of clinical activity of a p53 synthetic long peptide (p53‐SLP) vaccine, twenty patients with recurrent elevation of CA‐125 were included, eighteen of whom were immunized 4 times with 10 overlapping p53‐SLP in Montanide ISA51. The first 5 patients were extensively monitored for toxicity, but showed no ≥ grade 3 toxicity, thus accrual was continued. Overall, toxicity was limited to grade 1 and 2, mostly locoregional, inflammatory reactions. IFN‐γ producing p53‐specific T‐cell responses were induced in all patients who received all 4 immunizations as measured by IFN‐γ ELISPOT. An IFN‐γ secretion assay showed that vaccine‐induced p53‐specific T‐cells were CD4 + , produced both Th1 and Th2 cytokines as analyzed by cytokine bead array. Notably, Th2 cytokines dominated the p53‐specific response. P53‐specific T‐cells were present in a biopsy of the last immunization site of at least 9/17 (53%) patients, reflecting the migratory capacity of p53‐specific T‐cells. As best clinical response, stable disease evaluated by CA‐125 levels and CT‐scans, was observed in 2/20 (10%) patients, but no relationship was found with vaccine‐induced immunity. This study shows that the p53‐SLP vaccine is safe, well tolerated and induces p53‐specific T‐cell responses in ovarian cancer patients. Upcoming trials will focus on improving T helper‐1 polarization and clinical efficacy. © 2009 UICC