Preventive and therapeutic vaccination with PAP-3, a novel human prostate cancer peptide, inhibits carcinoma development in HLA transgenic mice.
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.
Machlenkin
Arthur
A
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Azriel-Rosenfeld
Ronit
R
Volovitz
Ilan
I
Vadai
Ezra
E
Lev
Avital
A
Paz
Adrian
A
Goldberger
Ofir
O
Reiter
Yoram
Y
Tzehoval
Esther
E
Benhar
Itai
I
Eisenbach
Lea
L
D000135:Acid Phosphatase; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000628:therapy; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008222:Lymphokines / Q000276:immunology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000276:immunology*; D017027:Protein Tyrosine Phosphatases / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use; D012795:Sialoglycoproteins / Q000276:immunology* / Q000627:therapeutic use
D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; C089422:Fv protein, human; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D008222:Lymphokines; D012795:Sialoglycoproteins; D000135:Acid Phosphatase; C428439:prostatic acid phosphatase; D017027:Protein Tyrosine Phosphatases