TRASTUZUCRAD

Oncolytic adenoviruses expressing monoclonal antibody trastuzumab for treatment of Her-2+ cancer

Coordinatore	HELSINGIN YLIOPISTO    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Finland [FI]
Totale costo	1˙622˙360 €
EC contributo	1˙622˙360 €
Programma	FP7-IDEAS-ERC Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	ERC-2007-StG
Funding Scheme	ERC-SG
Anno di inizio	2008
Periodo (anno-mese-giorno)	2008-09-01   -   2014-08-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	HELSINGIN YLIOPISTO  Organization address address: YLIOPISTONKATU 4 city: HELSINGIN YLIOPISTO postcode: 14 contact info Titolo: Dr. Nome: Akseli Eetu Cognome: Hemminki Email: send email Telefono: 358919000000 Fax: 358919000000	FI (HELSINGIN YLIOPISTO)	hostInstitution	0.00
2	HELSINGIN YLIOPISTO  Organization address address: YLIOPISTONKATU 4 city: HELSINGIN YLIOPISTO postcode: 14 contact info Titolo: Ms. Nome: Tiina Cognome: Berg Email: send email Telefono: +359 9 191 25129 Fax: +359 9 191 23008	FI (HELSINGIN YLIOPISTO)	hostInstitution	0.00

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 Obiettivo del progetto (Objective)

'Metastatic breast, ovarian, gastric and esophageal cancer are currently incurable and therefore require new and innovative treatment approaches. The objective of this project is to construct oncolytic adenoviruses that code for trastuzumab (HerceptinR), a monoclonal antibody against tumor associated receptor Her2. Intravenous trastuzumab is already widely used for treatment of Her2 breast cancer, and is being actively studied for other tumor types that frequently feature Her2 amplification, including ovarian, gastric and esophageal cancer. We hypothesize that expression of the antibody from a virus will result in production of high, sustained concentrations of functional trastuzumab in situ. In comparison to conventional intravenous delivery, this might results in enhanced anti-tumor activity but reduced systemic exposure and side-effects. Further, a single injection of the virus might result in prolonged production of trastuzumab which might be cost-effective as intravenous trastuzumab is expensive. The viruses will be targeted for effective delivery to tumor cells through viral capsid modifications, and oncolytic cell killing will proceed only in p16/Rb pathway mutant tumor cells. Trastuzumab production will be coupled to virus replication. Further, trastuzumab is secreted into the surrounding tumor tissue for an effective “bystander effect”, ie. killing of neighboring tumor cells. In summary, we hypothesize that this approach will result in tumor cell killing through viral oncolysis, the anti-tumor activity of trastuzumab, and the potential synergy between the approaches. Further, high local concentrations might result in anti-tumor efficacy superior to efficacy seen with intravenous trastuzumab. These developments might eventually result in increased treatment options for patients with currently incurable Her2 cancers.'