MABTOX

"Generation and Evaluation of ""Next-generation"" Antibody-Toxin-Conjugates for Cancer Therapy"

 Coordinatore NBE-THERAPEUTICS GMBH 

 Organization address address: HOCHBERGERSTRASSE 60C TECHNOLOGIE
city: BASEL
postcode: 4057

contact info
Titolo: Dr.
Nome: Ulf
Cognome: Grawunder
Email: send email
Telefono: +41 616332230
Fax: +41 616332231

 Nazionalità Coordinatore Switzerland [CH]
 Totale costo 1˙346˙001 €
 EC contributo 1˙061˙000 €
 Programma FP7-SME
Specific Programme "Capacities": Research for the benefit of SMEs
 Code Call FP7-SME-2013
 Funding Scheme BSG-SME
 Anno di inizio 2013
 Periodo (anno-mese-giorno) 2013-10-01   -   2015-09-30

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    NBE-THERAPEUTICS GMBH

 Organization address address: HOCHBERGERSTRASSE 60C TECHNOLOGIE
city: BASEL
postcode: 4057

contact info
Titolo: Dr.
Nome: Ulf
Cognome: Grawunder
Email: send email
Telefono: +41 616332230
Fax: +41 616332231

CH (BASEL) coordinator 422˙380.00
2    ERA BIOTECH

 Organization address address: CALLE BALDIRI REIXAC 15-21
city: BARCELONA
postcode: 8028

contact info
Titolo: Dr.
Nome: Miriam
Cognome: Bastida
Email: send email
Telefono: +34 934039783

ES (BARCELONA) participant 284˙435.00
3    TUBE PHARMACEUTICALS GMBH

 Organization address address: LEBERSTRASSE 20
city: WIEN
postcode: 1110

contact info
Titolo: Dr.
Nome: Wolfgang
Cognome: Richter
Email: send email
Telefono: +43 1740935100

AT (WIEN) participant 276˙615.00
4    PROTAGEN PROTEIN SERVICES GMBH

 Organization address address: OTTO HAHN STRASSE 15
city: DORTMUND
postcode: 44227

contact info
Titolo: Dr.
Nome: Martin
Cognome: Blueggel
Email: send email
Telefono: +49 23197426100

DE (DORTMUND) participant 16˙040.00
5    EVITRIA AG

 Organization address address: WAGISTRASSE 25-27
city: SCHIEREN
postcode: 8952

contact info
Titolo: Dr.
Nome: Markus
Cognome: Hildinger
Email: send email
Telefono: +41 435398815

CH (SCHIEREN) participant 14˙540.00
6    ONCOTEST GMBH PROF. DR. H. H. FIEBIG

 Organization address address: AM FLUGHAFEN 12-14
city: FREIBURG
postcode: 79108

contact info
Titolo: Dr.
Nome: Silvia
Cognome: Naus
Email: send email
Telefono: +49 7615155971

DE (FREIBURG) participant 12˙760.00
7    INNO TUNE BVBA

 Organization address address: VOORHOUTKAAI 20
city: GENT
postcode: 9000

contact info
Titolo: Mr.
Nome: Lieven
Cognome: De Smedt
Email: send email
Telefono: 3292244082

BE (GENT) participant 9˙040.00
8    BIOMEDAL SL

 Organization address address: CUBA 1-1B
city: SEVILLA
postcode: 41100

contact info
Titolo: Dr.
Nome: Angel
Cognome: Cebolla
Email: send email
Telefono: +34 954081276
Fax: +34 954081279

ES (SEVILLA) participant 8˙800.00
9    JPT PEPTIDE TECHNOLOGIES GMBH

 Organization address address: VOLMERSTRASSE 5 UTZ
city: BERLIN
postcode: 12489

contact info
Titolo: Dr.
Nome: Karsten
Cognome: Schnatbaum
Email: send email
Telefono: +49 3063927893

DE (BERLIN) participant 8˙800.00
10    TBD-BIODISCOVERY OU

 Organization address address: TIIGI 61B
city: TARTU
postcode: 50410

contact info
Titolo: Dr.
Nome: Olga
Cognome: Tsubrik
Email: send email
Telefono: +372 7477001

EE (TARTU) participant 7˙590.00
11    WESTFAELISCHE WILHELMS-UNIVERSITAET MUENSTER

 Organization address address: SCHLOSSPLATZ 2
city: MUENSTER
postcode: 48149

contact info
Titolo: Dr.
Nome: Katharina
Cognome: Steinberg
Email: send email
Telefono: 492518000000
Fax: 492518000000

DE (MUENSTER) participant 0.00

Mappa


 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

chemotherapy    generation    toxin    antibodies    mabtox    fda    adcs    homogeneous    selectivity    recently    manufacturing    first    drugs    expertise    transformed    potency    ratio    complementary    efficacy    standard    drug    conjugation    structure    technologies    site    regulatory    molecule    therapeutic    patients    approved    small    toxins    decade    cellular    therapy    cancer    last    antibody    cmc    enzymatic    addition    adc    chemical    coupling    conjugated    conjugates   

 Obiettivo del progetto (Objective)

'Therapeutic antibodies have transformed cancer therapy during the last decade, due to their high selectivity of targeting cancer cells in comparison to standard small molecule chemotherapy. Most recently, the coupling of cellular toxins to therapeutic antibodies has demonstrated an even greater efficacy in the therapy of cancer and the first, highly potent antibody drug conjugate (ADC), Adcetris®, was FDA approved in August 2011. All ADCs currently in clinical development are generated by chemical conjugation of small molecule toxins to antibodies. This is an inefficient process, as site and ratio of toxin coupling cannot be controlled. In addition, the chemical conjugation involves chemical modification of potentially functional parts of the antibody. This can have negative effects on stability, specificity, CMC properties and the overall structure of the antibody. All this renders ADC manufacturing highly challenging, complicates regulatory procedures, and adds to development time and costs. The SME consortium has complementary proprietary technologies and proposes to leverage this complementary expertise and know-how for defining novel processes of enzymatically conjugating small molecule toxins to antibodies that allow full control about toxin coupling site and ratio. Due to the high selectivity of enzymatic conjugation and physiologic conjugation conditions, it is expected that more homogeneous ADCs are generated with better CMC properties, higher potency, and at lower cost-of-goods in manufacturing. The consortium members believe that this represents a disruptive technology that will be highly competitive to traditional chemical conjugation, currently dominated by U.S.-based ADC technology companies Seattle Genetics and Immunogen. In addition to novel composition-of-matter IP, important novel know-how for ADC development will be created. Most importantly, better quality and potency of these “next-generation” ADCs will eventually benefit cancer patients.'

Introduzione (Teaser)

A European consortium is combining expertise to develop new technologies for the synthesis of improved antibody drug conjugates.

Descrizione progetto (Article)

Therapeutic antibodies against specific cancer antigens have transformed cancer therapy during the last decade. They exhibit high selectivity and fewer side-effects compared to standard small-molecule chemotherapy drugs. Recently, antibodies have been conjugated to cellular toxins, demonstrating even greater efficacy for the therapy of certain cancers. The first two antibody drug conjugates (ADCs) have been approved by the United States Food and Drug Administration (FDA) to treat Hodgkin's lymphoma and therapy-resistant HER-2+ breast cancer.

Traditionally, ADCs are generated by chemical coupling of small-molecular-weight toxins to free lysine or cysteine residues of the antibodies. However, this process cannot be controlled and results in a largely heterogeneous pool of ADCs of varying structure and efficacy. In addition, during chemical conjugation the 3D structure of antibodies, and hence their function, could be irreversibly damaged.

The scope of the EU-funded project 'Generation and evaluation of "next-generation" antibody-toxin-conjugates for cancer therapy' (http://www.mabtox.org/ (MABTOX)) is to develop novel enzymatic methods for the site-specific and controlled conjugation of toxins to ADCs. For this purpose, it has brought together small and medium-sized enterprises with expertise in antibody engineering, enzymatic conjugation and medicinal chemistry.

During the first part of the project scientists have successfully produced modified toxins and antibodies against known cancer targets. These recombinant molecules carry motifs that will serve as sites for enzymatic conjugation using two types of transpeptidases, the so-called intein and sortase enzymes. After successful generation of all components required for these novel enzymatic antibody conjugation methods, the consortium is ready to test this technology to produce next-generation ADCs.

It is now well established that better defined and homogeneous drugs are needed to enhance the safety, predictability and efficacy of ADCs for treating cancer patients and to obtain regulatory approval. MABTOX project partners hope to make this a reality through an enzymatic method that can deliver homogeneous ADCs with improved properties in comparison to their chemically conjugated counterparts.

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