Preventive and therapeutic vaccination with PAP-3, a novel human prostate cancer peptide, inhibits carcinoma development in HLA transgenic mice

Arthur Machlenkin, Ronit Azriel-Rosenfeld, Ilan Volovitz, Ezra Vadai, Avital Lev, Adrian Paz, Ofir Goldberger, Yoram Reiter, Esther Tzehoval, Itai Benhar, Lea Eisenbach

Research output: Contribution to journalArticlepeer-review

Abstract

Conventional treatment of recurrent and metastasized prostate cancer (CaP) remains inadequate; this fact mandates development of alternative therapeutic modalities, such as specific active or passive immunotherapy. Previously, we reported the identification of a novel highly immunogenic HLA-A*0201- restricted Prostatic Acid Phosphatase-derived peptide (PAP-3) by a two-step in vivo screening in an HLA-transgenic (HHD) mouse system. In the present study we aimed at elucidating the efficiency of PAP-3-based vaccine upon active antitumor immunization. To this end we established preventive and therapeutic carcinoma models in HHD mice. The 3LL murine Lewis lung carcinoma clone D122 transduced to express HLA-A*0201 and PAP served as a platform for these models. The HLA-A*0201-PAP-3 complex specific recombinant single chain scFV-PAP-3 antibodies were generated and used to confirm an endogenous PAP processing resulting in PAP-3 presentation by HLA-A*0201. PAP-3 based vaccines significantly decreased tumor incidence in a preventive immunization setting. Therapeutic vaccination of HHD mice with PAP-3 led to rejection of early established tumors and to increase of mouse survival. These results strongly support a therapeutic relevance of the identified CTL epitope upon active antitumor immunization. The newly established carcinoma model presented herein might be a useful tool for cancer vaccine design and optimization.

Original languageEnglish
Pages (from-to)217-226
Number of pages10
JournalCancer Immunology, Immunotherapy
Volume56
Issue number2
DOIs
StatePublished - Feb 2007

Keywords

  • Antigens/peptides/epitopes
  • Experimental animal models
  • T cells
  • Tumor immunity
  • Vaccination

Fingerprint

Dive into the research topics of 'Preventive and therapeutic vaccination with PAP-3, a novel human prostate cancer peptide, inhibits carcinoma development in HLA transgenic mice'. Together they form a unique fingerprint.

Cite this