The HLA-A2-restricted PSMA peptide LLHETDSAV is poorly immunogenic in patients with metastatic prostate cancer

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.

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.

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-gamma 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.

Our results suggest that the PSMA peptide LLHETDSAV is poorly immunogenic in humans and that alternative prostate cancer antigens should be pursued.