Binding of prostate-specific membrane antigen to dendritic cells: a critical step in vaccine preparation

Cytotherapy
Stefano GarettoLina Matera

Abstract

Dendritic cell (DC)-based vaccines hold promise as a safe therapy for prostate cancer (PCa), and prostate-specific membrane antigen (PSMA) fulfils the requirements for a tumor-associated antigen (TAA) to be clinically effective. We evaluated the actual binding of selected HLA-A2-restricted PSMA peptides to HLA class I molecules on ex vivo-generated mature (m) DC. mDC were generated from peripheral monocytes of HLA-A2 normal donors. The PSMA peptides PSMA(711) (ALFDIESKV), PSMA(27) (VLAGGFFLL) and PSMA(663) (MMNDQLMFL) were selected based on computer-assisted prediction programs, documented CTL epitope activity or previous use in clinical trials. The model cell line T2 and the clinical grade (CD83+ CCR7+) mDC were pulsed with fluorescein (FL)-conjugated peptides and an anti-HLA-A2 monoclonal antibody (MAb) and analyzed. Flow cytometry analysis showed best binding efficiency to be by PSMA(27.) Confocal microscopy confirmed coincident fluorescence emission of HLA-A2 MAb and FL-PSMA(27). Virtual co-localization of PSMA(27) and HLA class I molecules was supported further by fluorescence resonance energy transfer (FRET) analysis. The clinical relevance of our findings has to be validated in vivo. The present report is the first to sc...Continue Reading

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Citations

Jan 15, 2013·Journal of Amino Acids·Jyothi Thundimadathil
Feb 21, 2013·International Journal of Urology : Official Journal of the Japanese Urological Association·Davide BrusaLina Matera

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