Identification of surface molecules with enzymatic and signaling proprieties as targets for mAb-immunotherapy of human prostate cancers
Gianluca
Zaccarello1*,
Andrea
Zitella2,
Valeria
Quarona1,
Lorenzo
Daniele3,
Giovanna
Chiorino4,
Marilena
Bellò5,
Alessandro
Tizzani2,
Alberto
L.
Horenstein1, 6,
Gianni
Bisi5,
Fabio
Malavasi1 and
Fabio
Malavasi1*
-
1
University of Torino, Department of Medical Sciences, Italy
-
2
Città della Salute e della Scienza Hospital, University of Torino, Department of Urology, Italy
-
3
University of Torino, Città della Salute e della Scienza Hospital, Department of Biomedical Sciences & Oncology, Italy
-
4
Fondo Edo Tempia, Italy
-
5
University of Torino, Città della Salute e della Scienza Hospital, Department of Nuclear Medicine, Italy
-
6
Research Center on Experimental Medicine (CeRMS), Italy
We developed a panel of murine monoclonal antibodies (mAb) for diagnosis and therapy of human prostate cancers by selecting targets with enzymatic and/or signaling proprieties. mAb selection was made by exploiting different approaches on fresh and prostate cells). The selection grid lead to the selection of mAbs tested for their ability to modulate the transcriptome of the LNCaP line. Out of these, one was characterized as an anti-PSMA, a glycoprotein provided with enzymatic activities of N-acetylated α-linked acidic dipeptidase (NAALADase) and also of pteroyl poly-γ-glutamyl carboxypeptitdase (i.e., folate hydrolase). The molecule is homologous with the transferrin 1 and 2 receptors. The anti-PSMA mAb was efficiently used for radio-immumoscintigraphy in mice bearing a human prostate tumor. In vitro mAb ligation did not induce significant variations in the transcriptome on LNCaP, as tested by microarray.
Other reagents selected were agonistic mAb regulating gene activation. GF/3E8 modulates the expression of genes involved in carcinogenesis, metastatic spreading and transcription of cancer biomarkers.
GF/3D3 and C5 mAbs bind a 60 kDa heat-shock protein.
This study has enriched the armamentarium of mAbs specific for human prostate. The ongoing efforts are to use the regents non giving activatory signals as carriers of radioactive tracers (or toxins), ideal tools to trace primary and secondary lesions. Next step of the project is to use of the enzymatic characteristic of PSMA to convert pro-drug in to activate in situ anti-cancer drugs. Ambitious goal will be to use agonistic mAb for differentiation therapies or to induce cell death.
Keywords:
prostate cancer,
cancer immunotherapy,
Prostate Specific Membrane Antigen (PSMA),
radio-immumoscintigraphy,
Monoclonal antibody
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Translational immunology and immune intervention
Citation:
Zaccarello
G,
Zitella
A,
Quarona
V,
Daniele
L,
Chiorino
G,
Bellò
M,
Tizzani
A,
Horenstein
AL,
Bisi
G,
Malavasi
F and
Malavasi
F
(2013). Identification of surface molecules with enzymatic and signaling proprieties as targets for mAb-immunotherapy of human prostate cancers.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.01197
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Received:
15 Jul 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Gianluca Zaccarello, University of Torino, Department of Medical Sciences, Torino, Italy, gianluca.zaccarello@unito.it
Prof. Fabio Malavasi, University of Torino, Department of Medical Sciences, Torino, Italy, fabio.malavasi@unito.it