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Enhance the homogeneity, potency, and safety of your antibody-drug conjugates (ADCs) thanks to ProteoGenix’s flexible and diversified antibody-drug conjugate service platform. Drawing from 20+ years of experience in ADC development, our platform allies the high productivity of the XtenCHOᵀᴹ cell line with the high efficiency of click chemistry for antibody conjugation and robust bioanalytical methods. Obtain high-quality ADC products with up to 90% of antibodies conjugated with the desired drug-to-antibody (DAR) ratio.
Flexible conjugation strategies
Choose between chemical (cysteine and lysine) and click chemistry conjugation methods according to your unique needs
Drug diversity and dual drug ADC development
Choose the best drug for an optimal therapeutic efficacy or opt for dual drug systems thanks to our click chemistry platform for a synergist treatment
Keep full ownership of the antibodies developed for your ADC applications
Accelerated antibody production
Seep up ADC development and antibody engineering (affinity, click chemistry…) thanks to our highly productive cell line – XtenCHOᵀᴹ
Extensive bioanalytical capabilities
Characterize DAR values, drug load distribution, % of free drug and antibody with high accuracy and precision to ensure high success rates during clinical development
Solid track record
Benefit from 20+ years of experience in antibody-drug conjugate (ADC) development a 5 therapeutic ADCs in clinical trials
Vast range of complimentary services
Streamline ADC development thanks to our flexible solutions in antibody discovery (phage display, hybridoma), engineering (affinity, stability), and stable cell line generation
I. Preliminary phase (optional)
Payload Selection and ADC Development
ADC Optimization and Bioanalysis
– The desired DAR
– Overall antibody quality
ADC Is Delivered
High Productivity (scale-up) Stable Cell Line Development (Optional)
Antibody-drug conjugates (ADCs) are a category of biopharmaceutical drugs engineered as precise, targeted therapies for cancer treatment. Distinguished from traditional chemotherapy, ADCs are designed to selectively seek out and eliminate tumor cells, while preserving the well-being of healthy cells.
Our antibody-drug conjugate service can vary significantly in cost depending on several factors. Our prices start at a few thousand euros and scale upward depending on project complexity. The final cost is influenced by factors such as the source of the antibody and or antigen – whether provided by you or produced by our expert team at ProteoGenix. Additionally, the chosen approach for conjugation, be it chemical or enzymatic linkage, plays a role in determining the overall cost.
We are committed to providing transparent and fair pricing, enabling you to access high-quality ADC development services without breaking the bank. Unlock the therapeutic potential of your antibody with our cost-effective ADC development solutions. Trust in ProteoGenix’s extensive 20+ years of experience, where we prioritize delivering exceptional results while keeping your budget in mind.
At ProteoGenix, we understand that timing is everything. That’s why we aim to complete each ADC conjugation service in a timely manner with the highest priority. The duration of the process largely hinges on the specific conjugation approach selected for your project. Typically, the timeline can vary from a few weeks to several months, depending on various factors.
However, the antibody-drug conjugate
service timeline can be streamlined by providing the antibody sequence to our antibody experts, if available. In such cases, the process may take a few weeks, as we can readily proceed with the ADC development using your provided antibody.
On the other hand, if the antibody needs to be produced or developed by ProteoGenix, the timeline may extend to a few months. Our experienced team will work diligently to ensure the efficient production and characterization of each antibody before advancing to the ADC conjugation phase.
Rest assured that regardless of the timeline, our priority is delivering reliable, high-quality ADC solutions that align with your research or therapeutic objectives. We are committed to working closely with you throughout the development process as our Ph.D. account managers stay on constant communication about the progression of each project.
We offer two distinct approaches for each ADC conjugation service: chemical conjugation or enzymatic conjugation. Each method holds unique principles that play a pivotal role in determining the most suitable strategy for your specific project.
Chemical conjugation involves the covalent attachment of payloads to antibodies using specialized chemical linkers. On the other hand, enzymatic conjugation leverages enzymatic reactions to achieve the conjugation of payloads to antibodies.
Understanding the differences between these approaches is crucial for making an informed decision. Below is a table comparing key differences between chemical conjugation and enzymatic conjugation.
Several factors influence the choice of conjugation strategy using our antibody-drug conjugation service. First and foremost, the customer’s budget is a critical consideration. While enzymatic conjugation may be faster than chemical conjugation, the latter can offer distinct advantages for specific applications.
The timeline of the customer’s project is also a key factor. Enzymatic methods, due to their swifter nature, may be preferred for time-sensitive projects. Additionally, whether the customer provides the antibody or requires ProteoGenix to develop and produce it can impact the choice of strategy.
The number of linkers and payloads, as well as the desired Drug-to-Antibody Ratio (DAR), also influence the selection. Different strategies may yield varying results in terms of efficiency and performance, which is why we generally recommend testing both approaches in parallel.
At ProteoGenix, our expert team is dedicated to guiding you through this decision-making process through our free consultation service. We work closely with you to understand your unique requirements and objectives, ensuring that the chosen conjugation strategy aligns seamlessly with your project goals.
ProteoGenix’s antibody experts are committed to delivering ADCs of exceptional quality and performance that can only be maintained by rigorous quality control protocols. Our antibody-drug conjugate service offers a comprehensive bioanalysis of ADCs designed to ensure the highest standards are met throughout the development process.
ADCs consist of the following components:
These complex molecules combine the specificity of immunotherapies with the potency of cytotoxic agents. In the past decades, ADCs have found great success in the treatment of cancer, particularly, hematological conditions. With the continued improvement of linker chemistry and conjugation methods, ADCs will soon be viable tools to fight a larger number of malignancies.
Given the structure of ADCs, they are designed to target membrane-bound receptors that are abundant, specific to cancer cells, and efficiently recycled after cellular internalization. The major mechanism of action of ADCs involves the following steps:
An alternative mechanism of action relies on the release of the payload in the tumor microenvironment. With the use of cleavable linkers, it is possible to trigger the release of the payload via chemical signals, conditions, or enzymes. By releasing the payload in the extracellular matrix, cytotoxic agents are free to diffuse more quickly through solid tumors, thus averting the antigen barrier, and targeting cancer cells with significant mutations in the selected receptor (bystander effect).
The continued refinement of linker chemistry and conjugation methods is paving the way for ADCs to become effective tools in combatting a wider range of cancer types. With ongoing research and clinical trials, ADCs hold immense promise in offering more precise, less toxic, and potentially life-saving treatments for cancer patients.
Multiple strategies have been developed to conjugate linker-payload pairs to antibody carriers. The efficiency of these methodologies directly influences the load and distribution of payloads along the antibody backbone and the heterogeneity of the resulting ADC.
Antibody-drug conjugation services use chemical linkers that connect the payload (cytotoxic drugs) to the monoclonal antibodies. Linkers consist of an antibody-binding and a payload-binding domain. Their properties heavily influence the stability, safety, aggregation profile, therapeutic widow, and mechanism of action of ADCs.
Linkers are broadly classified as cleavable or non-cleavable. A list of the most commonly used linkers can be found in the table below.
Selecting the best linker for a specific ADC ultimately depends on several factors including the abundance of the target antigen, toxicity of the payload, and nature of the tumor (solid versus hematological tumor). For instance, cleavable linkers are more suitable when targeting low abundance target and solid tumors, given that these linkers are able to release their warheads on the tumor microenvironment allowing the rapid diffusion of the small drugs without the need for internalization.
Our antibody-drug conjugation service uses enzymes to link the payload (cytotoxic drugs) to monoclonal antibodies.
The best enzyme linkers for ADC development facilitate the targeted coupling of cytotoxic drugs to monoclonal antibodies. Enzymes create specific connections between the drug and the antibody, ensuring precise delivery to tumor cells while sparing healthy tissues.
This approach enhances the therapeutic efficacy and minimizes off-target effects, making it a promising strategy for advanced cancer treatments. Below are examples of enzymes used to link payloads to monoclonal antibodies.
Suitable payloads for ADCs are typically defined as efficient at killing cancer cells at the nanomolar and picomolar range. They also must be fairly soluble to avoid excessive aggregation, non-immunogenic, and possess reactive sites available for conjugation with a linker.
The major cytotoxic payloads belong to two families: tubulin inhibitors (maytansinoids, auristatins, or taxol derivates) and DNA-modifying agents (mainly calicheamicins). Most of these agents are also too toxic for system administration in a mono-therapeutic regimen. Tubulin inhibitors have an extensive and solid track record as payloads of ADCs. They act during the cell cycle, causing cell death via mitotic arrest. Most ADCs in the clinic carry tubulin inhibitors as payloads. In contrast, DNA-modifying agents can act independently of the cell growth cycle, causing the cleavage of the DNA molecule and leading to cell death by apoptosis.
More recently, alternative payloads such as camptothecin derivates and pyrrolobenzodiazepines (PBD) dimers have been gaining ground over more conventional drug classes.
What makes the bioanalysis of ADCs so challenging is the heterogeneous nature of these products – particularly relevant when conventional chemical conjugation methods (cysteine and lysine) are used. Heterogeneity is known to influence a number of ADC properties such as stability and therapeutic effectiveness, for this reason, extensive analysis of ADC products is essential to ascertain their success in later stages of development.
The major properties of ADCs and common bioanalytical methods used for their study include:
Of all the properties mentioned above, DAR and drug load distribution remain the most important. For their bioanalysis, the most widely used methods during early development include UV/Vis, HIC, and RP-HPLC, or LC-MS.
Due to the complexity and inherent heterogeneity of ADC products, it can be challenging to ensure their success during clinical development. However, focusing on optimizing a number of key properties is known to significantly increase their odds of receiving marketing approval:
Dozens of ADCs have reached the clinic since the approval of Mylotarg (gemtuzumab ozogamicin) in 2020. The current and future major cancer targets of these immunotherapeutics include:
The improvement of linker chemistry and conjugation strategies has been promoting the development of ADCs with different structures or mechanisms of action. Multiple trends are expected to mark the next generation of these complex biopharmaceuticals including:
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