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Potentiation of a p53‐SLP vaccine by cyclophosphamide in ovarian cancer: A single‐arm phase II study
Author(s) -
Vermeij Renee,
Leffers Ninke,
Hoogeboom BaukjeNynke,
Hamming Ineke L.E.,
Wolf Rinze,
Reyners Anna K.L.,
Molmans Barbara H.W.,
Hollema Harry,
Bart Joost,
Drijfhout Jan W.,
Oostendorp Jaap,
van der Zee Ate G.J.,
Melief Cornelis J.,
van der Burg Sjoerd H.,
Daemen Toos,
Nijman Hans W.
Publication year - 2012
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.27388
Subject(s) - elispot , cyclophosphamide , medicine , immunogenicity , immunology , interferon gamma , ovarian cancer , foxp3 , chemotherapy , cancer , immune system , gastroenterology , t cell
The purpose of the current phase II single‐arm clinical trial was to evaluate whether pretreatment with low‐dose cyclophosphamide improves immunogenicity of a p53‐synthetic long peptide (SLP) vaccine in patients with recurrent ovarian cancer. Patients with ovarian cancer with elevated serum levels of CA‐125 after primary treatment were immunized four times with the p53‐SLP vaccine. Each immunization was preceded by administration of 300 mg/m 2 intravenous cyclophosphamide as a means to affect regulatory T cells (Tregs). Vaccine‐induced p53‐specific interferon‐gamma (IFN‐γ)‐producing T cells evaluated by IFN‐γ ELISPOT were observed in 90% (9/10) and 87.5% (7/8) of evaluable patients after two and four immunizations, respectively. Proliferative p53‐specific T cells, observed in 80.0% (8/10) and 62.5% (5/8) of patients, produced both T‐helper 1 and T‐helper‐2 cytokines. Cyclophosphamide induced neither a quantitative reduction of Tregs determined by CD4 + FoxP3 + T cell levels nor a demonstrable qualitative difference in Treg function tested in vitro . Nonetheless, the number of vaccine‐induced p53‐specific IFN‐γ‐producing T cells was higher in our study compared to a study in which a similar patient group was treated with p53‐SLP monotherapy ( p ≤ 0.012). Furthermore, the strong reduction in the number of circulating p53‐specific T cells observed previously after four immunizations was currently absent. Stable disease was observed in 20.0% (2/10) of patients, and the remainder of patients (80.0%) showed clinical, biochemical and/or radiographic evidence of progressive disease. The outcome of this phase II trial warrants new studies on the use of low‐dose cyclophosphamide to potentiate the immunogenicity of the p53‐SLP vaccine or other antitumor vaccines.