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Immunotherapy is a treatment that activates or modifies the immune system to target and eliminate diseases, especially cancer, by enhancing the body’s natural defenses to recognize and attack cancer cells. ADC immunotherapy is a targeted cancer treatment that combines the specificity of monoclonal antibodies with the potency of cytotoxic drugs.
Designed to selectively target and kill cancer cells, ADCs utilize antibodies that bind to specific antigens on the surface of tumor cells, allowing the ADC to deliver a powerful drug payload directly into the cancer cell. This targeted approach reduces off-target toxicity and minimizes damage to healthy cells, enhancing treatment efficacy and patient safety. ADC immunotherapy represents a significant advancement in oncology, offering new options for difficult-to-treat cancers and showing potential in combination with other immunotherapies for improved clinical outcomes.
Antibody-drug conjugates (ADCs) represent an important class of new biopharmaceutical modalities. ADCs are highly complex and heterogeneous molecules, potentially containing numerous product-related structures, that can contribute to the quality, efficacy and safety of the product. Most ADCs are synthesized by conjugating a cytotoxic compound or payload to a tumor specific monoclonal antibody. The payloads are conjugated using amino or sulfhydryl specific linkers that react selectively with lysines or cysteines on the antibody surface. ADC therapy is shifting from hematomas (lymphoma and leukemia) to solid tumors (such as breast, urethral, lung, and ovarian cancer), and the expansion of these clinical indications also highlighted the therapeutic potential of ADCs. In order to enable ADC drugs to function through all biological processes efficiently, antibodies, toxin molecules, linkers, and conjugation methods need to be considered when constructing ADCs.
During ADC development and production, payload (cytotoxic) selection is critical. We need to consider a variety of factors, including solubility, conjugation suitability, stability, and potency. At the same time, it is necessary to ensure that the drug is hydrophilic enough to conjugate with the antibody under aqueous conditions, and to ensure the stability of the resulting conjugate. Considering the low solubility of many potential drugs, this can be improved using hydrophilic linkers. Additionally, one needs to ensure that the payload carries an appropriately chemically functional handle, such as an amine, to allow binding to the antibody. Drug classes based on clinically approved ADCs include calicheamicins, mertansines , auristatins and camptothecins.
Linkers play a crucial role in the preparation of ADCs. First, the linker ensures a stable binding between the drug and the antibody, thereby preventing premature release of the drug during circulation. Secondly, when the ADC is localized to disease cells, the linker can promote the release of the drug. Based on their release mechanisms, linkers can be divided into two categories: cleavable linkers and non-cleavable linkers. Non-cleavable linkers rely on degradation of the antibody after endocytosis into lysosomes, thereby releasing the drug while the linker remains covalently attached, such as Kadcyla. In contrast, cleavable linkers are more common, and their drug release mechanisms include acidic pH hydrolysis, thiol reduction, and protease cleavage.
Monoclonal antibodies are the targeting agents in ADC therapy. Successful development of antibodies for ADC therapy first requires the identification of antigens that are ubiquitous on target cells but absent in normal tissues, in order to be able to specifically target tumors. During past research and development, it was discovered that severe ADC side effects may be caused by antigen expression on unrelated cell types. For example, HER2 expression in cardiac tissue can contribute to cardiotoxicity of trastuzumab-based ADCs. The majority of antibodies in approved ADCs belong to the IgG1 isotype, with IgG4 being the second isotype used (e.g. Mylotarg and Besponsa).
The selection of target antigens is a key factor in the successful development of ADC drugs. Targets serve as the primary means by which ADC drugs recognize tumor cells and are internalized, impacting drug efficacy and the competitive landscape. An ideal target should have the following characteristics:
Currently, 15 approved ADC drugs target 11 specific antigens, including CD33, CD30, HER2, CD22, CD79b, Nectin-4, BCMA, EGFR, CD19, Tissue Factor, and FRα. Statistics show that among the 425 ADC drugs under development, popular targets include HER2, EGFR, CLDN18.2, TROP2, c-Met, CD19, PSMA, Muc1, BCMA, and PDL1, most of which are well-validated targets.
| AXL Targets | CD22 Targets | CD79b Targets | FOLR1 Targets | ROR1 Targets |
| BCMA Targets | CD30 Targets | c-MET Targets | HER2 Targets | TF Targets |
| CD19 Targets | CD33 Targets | EGFR Targets | Nectin-4 Targets | TROP-2 Targets |
As of 2024, the U.S. Food and Drug Administration (FDA) has approved several ADCs for treating various malignancies, including breast cancer, non-small cell lung cancer, and lymphoma. Each ADC targets cancer cells through its specific antibody, then releases a potent cytotoxic drug to induce cancer cell death. Approved antibody drug conjugates include T-DM1 (Kadcyla), Brentuximab vedotin (Adcetris), and Enfortumab vedotin (Padcev). The FDA’s continued approvals and advancements in technology highlight a promising future for ADCs in cancer therapy. However, these drugs still face challenges such as production complexity and high costs, with researchers working to optimize their efficacy and safety for broader, more affordable clinical use.
Since the approval of the first ADC in 2000, ongoing efforts have focused on designing novel ADCs with improved efficacy and reduced toxicity. These efforts are reflected in the number of ADCs currently in active trials, representing just a portion of all ADC research. To date, over 260 ADCs have been tested clinically across various oncology indications. In addition to the 15 ADCs currently approved by the FDA, there are 164 in clinical trials and 92 candidates that were discontinued following clinical testing. These trials focus on optimizing drug-to-antibody ratios, linker stability, and payload delivery to enhance therapeutic outcomes and safety profiles.
BOC Sciences' one-stop service platform not only provides ADC products, but also provides ADC payload and linker development services for your scientific research and production. We can not only provide high specificity and high affinity personalized antibody modification and conjugation technology in a short time, but also provide ADC cGMP manufacturing, ADC purification, ADC filling, ADC analysis and characterization services according to customer needs.
ADC linker-cytotoxin compounds and coupling methods are the core elements of ADCs. In the whole ADCs construction, the core part that is easy to produce differences is the combination part of linkers and cytotoxins, and the conjugation with antibodies. ADCs combine the macromolecules and small molecules characteristics. The production and preparation process mainly includes monoclonal antibody preparation, linker development, small molecule drug preparation, ADCs conjugation, purification and finished product production, which leads to the complexity of its production process. It also makes the analysis, design and manufacturing of its structure face great challenges.
ADC analysis services offer precise analytical solutions to ensure the quality, stability, and efficacy of ADCs. These services include in-depth assessment of critical parameters such as drug-to-antibody ratio (DAR), conjugation site analysis, and payload distribution, using advanced techniques like mass spectrometry, chromatography, and electrophoresis. ADC Characterization also evaluates factors like aggregation, structural integrity, and in vitro binding affinity, crucial for clinical performance. These detailed analyses help in optimizing ADC design, monitoring batch consistency, and meeting regulatory standards, ensuring safe and effective therapeutic outcomes.
One-stop service for ADC bioanalysis: ELISA, ECLA, LC-MS/MS, LBA
Total antibody, conjugated antibody, free cytotoxin, immunogen analysis
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AntibodyThe final construction of the ADC requires conjugation of linkers and drugs to native antibodies. Currently, there are two coupling methods in FDA-approved ADC products: (1) lysine conjugation and (2) cysteine conjugation.
In lysine conjugation, the activated N-hydroxysuccinimide ester on the linker reacts with nearby lysine residues on the ADC surface to generate a stable amide bond. Likewise, natural cysteine is often used for conjugation. First, interchain disulfide bonds are reduced to provide free cysteines for conjugation. Next, the side chain thiol undergoes a Michael addition reaction to combine with the electrophilic acryloyl group in the linker with a maleimide pendant, forming a stable linkage. Potential advantages of cysteine conjugation include more controllable drug-to-antibody ratios (DAR) and a more uniform product.
BOC Sciences is a leading supplier of ADC products, offering a variety of ADC cytotoxins, linkers, linker with cytotoxins, and fully assembled ADCs. With years of experience in chemical synthesis and drug development, we have become a reliable and trustworthy source for high-quality ADC products.
One of the key strengths of BOC Sciences is our extensive catalog of ADC cytotoxics. These cytotoxins are potent drugs designed to selectively kill cancer cells when delivered through an antibody-targeting mechanism. We offer a variety of cytotoxics with different mechanisms of action and potencies, allowing researchers to choose the most appropriate option for their specific needs. Some popular ADC cytotoxics include maytansinoids, auristatins, and duocarmycins.
In addition to ADC cytotoxics, we offer a variety of ADC linkers. Linkers are an important component of ADCs as they are responsible for linking cytotoxins to antibodies. BOC Sciences offers a variety of linker types, including cleavable linkers, non-cleavable linkers, and self-immolative linkers. These linkers can be customized to meet the specific requirements of each ADC project, ensuring maximum efficacy and safety.
In addition, BOC Sciences offers ADC cytotoxics with linkers, which are preconjugated products for use in ADC development. These products eliminate the need for researchers to synthesize their own cytotoxin-linker conjugates, saving time and resources. Our linker ADC cytotoxics are rigorously tested for purity and potency to ensure consistent performance in preclinical and clinical studies.
BOC Sciences offers fully assembled ADCs that are fully functional antibody drug conjugates ready for research and development. These ADCs are constructed using high-quality antibodies and cytotoxins to ensure optimal targeting and efficacy against cancer cells. BOC Sciences fully assembled ADCs are ideal for screening assays, target validation studies and therapeutic development.
