Dott.ssa Simona Cignetto
- f502-c003 Dottorato in Medicina Molecolare
- Dottorato: 27° ciclo
- Matricola: 304914
Tesi di dottorato
STRATEGIES TO IMPROVE HALF-LIFE AND POTENCY OF A MET THERAPEUTIC ANTIBODY.
My PhD thesis talks about two different strategies to improve stability and subsequent potential of a Fab fragment derived from a monoclonal antibody directed against the extracellular portion of Met, which is highly expressed and activated in lot of tumors.
We needed to obtain the Fab fragment from the full-size antibody because of its capability to activate Met inducing its dimerization, due to its bivalent form. The Fab portion demonstrated to be deprived of the native agonistic activity and to be able to exert a fully antagonistic activity, inducing the downregulation of the receptor.
The disadvantage of the Fab was its short plasma stability, due to its low molecular weight.
Our strategies were based on the increase of the Fab molecular weight: the first one involved the traditional PEGylation, the second one the generation of newly recombinant proteins with a design developed by our group.
Attività di ricerca
- Development, analysis and validation of new engineered antibodies (Dual-Constant-Domain Fabs) for anti-Met targeted therapy;
- Antibody-based anti-Met gene therapy;
- Met as target of an antibody-based anti-cancer therapy
- Vigna E, Pacchiana G, Chiriaco C, Cignetto S, Fontani L, Michieli P, Comoglio PM. Targeted therapy by gene transfer of a monovalent antibody fragment against the Met oncogenic receptor. J Mol Med 2013
- Vigna E, Chiriaco C, Cignetto S, Fontani L, Basilico C, Petronzelli F, Comoglio PM. Inhibition of ligand-independent constitutive activation of the Met oncogenic receptor by the engineered chemically-modified antibody DN30. Mol Oncol. 2015
- Cignetto S, Chiriaco C, Fontani L, Modica C, Arpicco S, Milla P, Comoglio PM and Vigna E. Dual Constant Domain-Fab: a novel strategy to improve half-life and potency of a Met therapeutic antibody. Mol Oncol. Under revision.
- European Cancer Congress 2013 (ECCO17-ESMO38-ESTRO32), 27 September-1 October 2013, Amsterdam RAI Exhibition and Convention Centre - Amsterdam (NL)
- 2014 International Conference on Molecular Clinical Oncology “Precision Medicine”, 4-5 October 2014, Candiolo Cancer Institute - Candiolo (TO-Italy)
- Frontiers in Regenerative Medicine, 18-20 February 2015, Molecular Biotechnology Center – Torino (Italy)
- 2015 International Conference on Molecular Oncology, 6-7 June 2015, Candiolo Cancer Institute - Candiolo (TO-Italia)