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ANTIBODY-DRUG CONJUGATE DEVELOPMENT

Home/Therapeutic antibody / ADC development

ProteoGenix combines the most renowned antibody-drug conjugates experts and a long-lasting experience in antibody development in order to offer best-in-class ADC development services. Don’t miss to reach the clinic and work with the service provider with the strongest track record in therapeutic antibodies on the market!

Why choose ProteoGenix for your antibody-drug conjugate development?

ADC antibody experts
Antibody-drug conjugates expert

Trust our expertise of 20+ years in antibody-drug conjugate (ADC) development and 2 ADCs in clinical phases.

Optimized developability parameters

Benefit from our integrated solutions from antibody generation to stable cell line development to get an ADC with optimized developability parameters.

IP free antibody drug conjugate
IP free

Our antibody-drug conjugate development solutions are IP free. You keep the full ownership of the antibodies developed.

ISO antibody-drug conjugates platform
ISO 9001 certification

Our services are ISO 9001:2015 certified. This reflects our commitment to propose antibody production services with the highest quality standards at every level.

Antibody drug conjugate characterization
Full set of characterization

We provide fully characterized antibody-drug conjugates including DAR, DAR distribution, drug location, % free drug as well as all the classical antibody QC measurement.

ADC development managers
PhD account managers

As antibody-drug conjugate development requires extended scientific skills and knowledge, we put at your disposal PhD account managers who will assist you all along.

ProteoGenix' antibody-drug conjugate (ADC) development flowchart

ADC antibody engineering
Antibody engineering
  • Antibody production with optimized affinity
  • Site-directed mutagenesis for site-specific conjugation
antibody drug conjugates(ADC) linker and drug
Linker and drug procurement
  • Off the shelf
  • Customer provided
  • Custom synthesis
Antibody conjugation
  • Antibody conjugation with the coupling chemistry defined in early stage.
  • Purification
Antibody-drug conjugate characterization
  • DAR: HIC chromatography
  • DAR distribution: HIC chromatography
  • Site of payload conjugation: RP-HPLC
  • % free drug: RP-HPLC
  • % aggregation: SEC-HPLC
  • Endotoxin level detection/removal
  • Binding analysis: ELISA, antibody KD determination
  • Stability: differential scanning calorimetry
  • Other QC analysis available under request
Antibody-drug conjugate final product

In addition to this process, ProteoGenix can perform a preliminary study for the selection of the optimized parameters such as:

  • Antibody/ linker/ payload nature

  • DAR

  • Payload location

  • Additional parameters

You need to develop an antibody-drug conjugate (ADC) and want to discuss your project with our PhD account managers ? Please feel free to contact us!

What are the key factors to consider in antibody-drug conjugate development?

Antibody-drug conjugates(ADC) allow the specific targeting of highly potent drugs which could not be delivered as mono-therapy. Even if the concept remains simple and particularly attractive for therapeutic antibody development development, the success of an ADC development is related to a careful control of several factors. Here, we summarize some of the key factors to consider to increase your chances to reach clinical phases:

ANTIBODY AFFINITY

Once a highly specific target has been chosen, a humanized antibody with optimal affinity should be produced. One would consider that the highest the affinity, the better the antibody-drug conjugate. However, this is rarely true. For instance, high affinity antibodies can have a positive effect on the internalization rate but limits solid tumor penetration due to site-barrier effect. Thus, optimal antibody affinity has to be determined depending on the therapeutic application.

LINKER STABILITY

The linker is a crucial component of an antibody-drug conjugate as it covalently tethers the antibody and the payload. Properties of a good linker include:

  • Stability in blood circulation to prevent the release of the payload and side effects
  • Specific and fast release of the payload into the target cells

DRUG-ANTIBODY RATIO (DAR)

The drug-antibody ratio is of critical importance in antibody-drug conjugate development as differences in drug loading can induce modifications in terms of toxicity and/or therapeutic index. Following some studies, a DAR of 4 is considered as an optimum for anti-cancer activities. Higher DAR is considered in case of low-expression tumor antigens or slow internalization kinetics but demonstrates a higher propensity for aggregation and clearance. In any case, several DAR should be tested to find optimal therapeutic efficacy.

DAR DISTRIBUTION

A broad DAR distribution negatively impacts toxicity and therapeutic efficacy. A narrow DAR distribution allows for better control of payload loading.

AGGREGATION

As for all antibodies, aggregation can affect immunogenicity and therapeutic efficacy of an ADC. ADCs with high DARs are more prone to aggregation due to the hydrophobic nature of payloads.

% FREE DRUG

ADC’s payloads are highly potent and could not be delivered as mono-therapy. In order to ensure safety, % free drug should be as low as possible.

Conjugation strategies for antibody-drug conjugate development

Conjugation strategy remains an essential question when developing an ADC because it directly influences the drug-antibody ratio (DAR) as well as the DAR distribution. Here is an overview of the coupling methods currently used for antibody-drug conjugate production.

CHEMICAL CONJUGATION

Chemical coupling is the most used conjugation strategy in antibody-drug conjugate development. Up to date, all the FDA approved antibody-drug conjugates are based on these technologies. Chemical conjugation can be performed on native residues or can be controlled by the introduction of genetically engineered sites.

The use of natural amino acids for conjugation is an attractive solution as it does not request any antibody engineering. Conjugation occurs via solvent accessible lysine or cysteine residues which contain reactive primary amines or thiols, respectively. DAR and DAR distribution can be better controlled for cysteine coupling due to the lower occurrence of accessible cysteine residues in the antibody structure.

Site-specific conjugation offers an even more controlled alternative. This conjugation method can use genetic engineering in order to introduce free cysteine residues to the antibody structure.

ENZYMATIC COUPLING

Site-specific coupling can also be obtained using enzymatic conjugation on native or engineered antibodies. Sortase A or transglutaminase are example of enzymes able to modify the antibody in a site-specific manner.

Examples of engineering of the conserved N-glycan from the Fc region are also available in the literature using galactosyltransferase.