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The HLA‐A2‐restricted PSMA peptide LLHETDSAV is poorly immunogenic in patients with metastatic prostate cancer
Author(s) -
Knight David,
Peterson Amy C.,
Rini Brian I.,
Harlin Helena,
Gajewski Thomas F.,
Stadler Walter M.
Publication year - 2008
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20864
Subject(s) - elispot , immunogenicity , prostate cancer , medicine , immune system , immunology , antigen , peripheral blood mononuclear cell , epitope , peptide vaccine , immunotherapy , human leukocyte antigen , t cell , prostate specific antigen , cancer , ex vivo , biology , in vivo , in vitro , biochemistry , microbiology and biotechnology
Background Increasing evidence suggests that prostate cancer is visible to the immune system and is potentially responsive to immunotherapeutic interventions. Previous work has identified prostate‐specific membrane antigen (PSMA) as a potential antigen for T‐cell recognition, and specific PSMA epitopes presented by HLA‐A2 have been described. One vaccination strategy that is being pursued in the clinic utilizes peptide‐pulsed peripheral blood mononuclear cells (PBMC) + IL‐12. Methods HLA‐A2 + patients with castrate‐resistant prostate cancer and normal organ function were considered. Vaccines were prepared using autologous PBMC loaded with a PSMA peptide previously reported to be immunogenic (LLHETDSAV) administered subcutaneously every 3 weeks. T‐cell responses and tumor activity were assessed. Results Although the vaccine was well tolerated, no clinical responses were observed in 12 enrolled patients and no immune responses were detected based on an ex vivo IFN‐γ ELISPOT assay. To examine immunogenicity of this PSMA peptide in more detail, an in vitro priming assay was utilized with normal donor PBMC, and no detectable reactivity was observed. Conclusions Our results suggest that the PSMA peptide LLHETDSAV is poorly immunogenic in humans and that alternative prostate cancer antigens should be pursued. Prostate 69: 142–148, 2009. © 2008 Wiley–Liss, Inc.