Anti-PSMA scFv as theranostic tool for Prostate cancer
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1
Fondazione IRCCS Istituto Nazionale Tumori, Italy
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2
univeristy of verona, Italy
Prostate carcinoma (PCa) is the most common malignant tumor diagnosed in men and the second leading cause of cancer related mortality. As a result of the limited efficacy of conventional treatments for advanced PCa, other strategies are needed. Antibody-based reagents represent a promising approach to provide the clinic with potentially effective diagnostic and therapeutic tools. To date, the most extensively tumor associate antigen studied for PCa immunotherapy is the Prostate-Specific Membrane Antigen (PSMA). PSMA expression and enzymatic activity are increased in PCa and are also correlated with aggressive disease.
The D2B monoclonal antibody directed against h-PSMA extracellular domain was produced by hybridoma technology. Preliminary diagnostic specificity of the IgGD2B has been investigated in xenograft murine models by imaging. Overall, the low penetration rate from vasculature into solid tumor mass and their prolonged residence in circulation limit the application of whole antibody for imaging or radio immunotherapy.
For these reasons we re-shaped the IgGD2B into scFv format. Due to its smaller size, scFv represents the ideal candidate as diagnostic reagent because shows a faster blood clearance and a better penetrability in the tissue. ScFvD2B functionality was successfully tested on PC3 cell line expressing h-PSMA and BIAcore showed that the antibody fragment retains a good strength of binding despite its monovalent binding.
For the potential use of scFvD2B for radioimaging we have firstly set the radiolabelling procedure with 131I and then we have performed the pre-clinical studies in animals bearing tumors expressing or non expressing PSMA with conventional radio localization experiments.
Acknowledgements
Partially supported by Fondazione Monzino, Fondazione Cariplo, AIRC 5x1000 Bombardieri, AIRC 5x1000 2010 IG 13121 , Fondazione Cariverona (Verona Nanomedicine Initiative and Interceptin project, AIRC 5x1000, Fondazione Cariverona/AIRC Progetto Regionale.
Keywords:
prostate cancer,
single chain Fv,
Prostate Specific Membrane Antigen,
imaging,
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:
Frigerio
B,
Luison
E,
Satta
A,
Bernareggi
D,
Caroli
F,
Fracasso
G,
Canevari
S and
Figini
M
(2013). Anti-PSMA scFv as theranostic tool for Prostate cancer.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00735
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Received:
18 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Mariangela Figini, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, mariangela.figini@istitutotumori.mi.it