ADC refers to a class of biotechnological drugs that conjugates small-molecule compounds to targeted antibodies or antibody fragments through linkers. Its structural components include an antibody or antibody fragment (Antibody), a linker (Linker), and a cytotoxic small-molecule compound (Payload).

Antibodies are key proteins in the immune system that specifically recognize and bind to antigens, such as unique proteins on the surface of tumor cells. In ADCs, monoclonal antibodies with high specificity and affinity are typically used. These antibodies specifically bind to tumor-associated antigens with high affinity, serving as carriers to deliver cytotoxic payloads directly to cancer cells. This targeted delivery enhances drug efficacy and minimizes damage to normal tissues.

The linker is a crucial component in ADC design, covalently attaching the antibody to the cytotoxic small molecule. It must be stable in circulation to prevent degradation before reaching the target organ, yet able to rapidly release the active payload once inside the cell to exert its therapeutic effect.

Linkers could be categorized into cleavable and non-cleavable types. Cleavable linkers break under specific conditions, such as acidic or reductive environments, to precisely release the ADC’s active component. Non-cleavable linkers require lysosomal or protease-mediated degradation of the antibody before releasing the payload.

The payload is the active cytotoxic component of ADCs, typically a small molecule with cell-killing properties, such as chemotherapeutic agents, radioactive isotopes, or bio-toxins. It is conjugated to the antibody via a linker and delivered specifically to target tumor cells. Once inside the cell, the payload exerts its cytotoxic effect, leading to cell death.

In addition to cytotoxicity, an ideal payload must exhibit plasma stability, low immunogenicity, appropriate molecular weight, and optimized pharmacokinetic properties. These attributes collectively determine the efficacy and safety of ADCs and are critical considerations in ADC drug development. Payloads are generally categorized into two major classes based on their targets.

Antibody-Drug Conjugates (ADCs) are rapidly evolving anticancer agents designed to enhance the therapeutic index (the ratio of the maximum tolerated dose to the minimum effective dose). This is a significant improvement over traditional cytotoxic chemotherapies, which often have a low therapeutic index. The core concept of ADCs is to use monoclonal antibodies as specific carriers to deliver cytotoxic payloads to target cancer cells while minimizing damage to normal cells. The process typically involves the following steps.

First, the ADC specifically binds to the antigen, forming an antigen-ADC complex that is rapidly internalized into endosomal vesicles (①-②). In this acidic and protease-rich environment, degradation occurs, leading to the release of the cytotoxic compound within the cell (③-④). A portion of the payload may also be released into the extracellular environment and subsequently taken up by neighboring cells through a bystander effect (⑤-⑦).

To facilitate the pharmacokinetic (PK) analysis of small-molecule toxins (payloads) in ADC drugs. These antibodies aid in the characterization, analysis, and efficacy assessment of ADC drugs. The pharmacokinetics of ADCs share many similarities with unconjugated monoclonal antibodies, such as long half-lives and low clearance rates. However, the conjugation of small-molecule drugs increases the heterogeneity of ADCs. Therefore, multiple analytes must be evaluated to reveal the PK characteristics of ADCs. The common analytes used to characterize the PK features of ADC drugs include: Conjugated antibody (antibody conjugated with at least one small-molecule toxin), Total antibody (both conjugated and unconjugated antibodies with small-molecule toxins), Conjugated small-molecule toxin, Free small-molecule toxin and its analogs.

In ADC pharmacokinetic (PK) studies, anti-payload antibodies can be used to monitor the concentration, distribution, and clearance rates of conjugated antibodies in the body. This information is crucial for optimizing dosing regimens and ensuring that ADCs reach their targets at appropriate concentrations. By combining ligand-binding assays (LBA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), a comprehensive evaluation of ADC PK characteristics can be achieved, including ADC heterogeneity, metabolic pathways, and metabolites.

In ligand-binding assays (LBA), anti-payload antibodies are commonly used as capture reagents to specifically capture antibodies conjugated with the payload (i.e., conjugated antibodies) from complex biological samples. This capture mechanism is based on the specific binding between antigen and antibody, which can efficiently separate conjugated antibodies from other unconjugated antibodies, free payload, or other biological matrices.

The drug-to-antibody ratio (DAR) quantifies the average number of cytotoxic payload molecules conjugated to each antibody, defining the drug-loading capacity of an ADC. It not only determines the drug payload but also significantly impacts the distribution, clearance rate (pharmacokinetic, PK, characteristics), and overall safety and efficacy of ADCs^[5]. Studies have shown that ADCs exhibit optimal therapeutic effects when the DAR value is between 2 and 4. Within this range, ADCs can balance efficacy and safety, ensuring sufficient drug molecules enter tumor cells while minimizing toxicity to normal cells. Increasing the DAR value enhances the concentration of toxic molecules in tumor cells, thereby improving tumor-killing capacity. However, excessively high DAR values can lead to drug aggregation, reducing targeting and efficacy. Moreover, high DAR values may increase the immunogenicity of ADCs, triggering immune system recognition and accelerating drug clearance. Therefore, accurate determination and monitoring of DAR value distribution are crucial in ADC development.

Anti-payload antibodies facilitate the detection of conjugated antibodies and the assessment of ADC DAR values. By comparing the ratio of captured conjugated antibodies to total antibodies, the distribution and average DAR can be estimated, which in turn allows for the evaluation of ADC homogeneity and potency.

1）DXd Antibody (YA897) : HY-P81054. Application：ELISA

Activity: Measured by its binding ability in a functional ELISA. Immobilized T-DXd(DS-8201) at 2 μg/mL can bind Anti-DXD Antibody, the EC50 is 1.120 to 1.566 ng/mL.

Activity: Measured by its binding ability in a functional ELISA. Immobilized Labetuzumab govitecan at 2 μg/mL can bind Anti-SN38 antibody, the EC50 is 2.755 to 3.388 ng/mL.

Activity: Measured by its binding ability in a functional ELISA. Immobilized Farletuzumab ecteribulin at 2 μg/mL can bind Anti-Eribulin antibody, the EC50 is 0.8888 to 1.027 ng/mL.

In recent years, the remarkable progress of antibody-drug conjugates (ADCs) has spurred a transformative trend in the realm of conjugated drug technologies—an era where "everything is conjugateable," commonly known as XDCs. At their core, XDC drugs adhere to a well-defined formula: a tumor-targeting delivery vehicle, a bioactive payload designed to elicit diverse therapeutic effects, and a linker that covalently bridges these two essential components.

We provide high-quality, high-affinity, and high-purity ADC antibodies and related products, covering a wide range of popular targets like HER2, EGFR, CD20, VEGFR, TNF-α, etc. These products can serve as positive controls for drug efficacy evaluation and other scientific research, fully supporting your preclinical studies. Moreover, our top-notch anti-payload antibodies not only significantly speed up the development of current ADC drugs but also show great potential in playing a more crucial and extensive role in the advanced exploration of XDCs.