Comparative Applications of ADC-Positive Drugs in Companion Diagnostics and Clinical Testing

Importance of Companion Diagnostics in ADC Therapy

The efficacy of antibody-drug conjugates (ADCs) is highly dependent on the specific expression level of the target on tumor cells. Companion diagnostic testing has therefore become a core tool for patient selection and treatment decision-making. For example, ADC drugs targeting HER2 require confirmation of HER2 status through immunohistochemistry (IHC) or in situ hybridization (ISH). In these testing workflows, the quality of positive controls directly affects the reliability of result interpretation. ADC positive drugs generally refer to cell lines or recombinant protein preparations with known positive target expression that have been fully validated, capable of stably reproducing the expected staining or binding signals.

ADC Positive Drugs as Immunohistochemistry Positive Controls

In IHC testing, ADC positive drugs are often prepared as tissue sections or cell wax blocks for use as negative and positive controls. For example, cell lines overexpressing the target antigen (such as SK-BR-3 for HER2) are co-embedded with cell lines not expressing the target antigen (such as MDA-MB-231) to establish a gradient of staining intensity. Such positive controls can help pathologists calibrate antibody dilution, retrieval conditions, and chromogenic development time, avoiding false negatives or false positives. According to medical device registration guidelines, companion diagnostic kits should include supporting positive control materials or recommend the use of validated ADC positive drugs as external controls. It should be noted that batch-to-batch consistency of positive controls should be monitored through established quality control thresholds (such as H-score or staining intensity grades).

Quality Control Applications in Flow Cytometry and ELISA

In hematological malignancy or liquid biopsy settings, flow cytometry is commonly used to detect target expression on circulating tumor cells or immune cells. ADC positive drugs can be prepared as fluorescently labeled microspheres or immobilized cells for gating setup and instrument calibration. Additionally, in enzyme-linked immunosorbent assay (ELISA), when detecting free ADC concentrations or anti-drug antibodies (ADA) in serum, ADC positive drugs can serve as the high point of the standard curve or as positive references. It is generally required that the drug-to-antibody ratio (DAR) distribution of the positive drug be similar to that of the actual administered formulation to reflect true binding kinetics.

Selection of Positive Controls for Different ADC Drug Types

For ADCs targeting different targets (such as TROP2, Nectin-4, CD30) and different linker types (such as vc-PABC, maleimidocaproyl), positive controls need to be customized accordingly. For example, for ADCs with enzyme-cleavable linkers, positive drugs need to verify the kinetics of toxin release in the tumor microenvironment. For ADCs with non-cleavable linkers, greater attention is paid to signal transition after internalization. In industry practice, some suppliers offer specialized ADC positive drug kits containing calibrated positive references and negative controls, and users must fully document batch information and expiration dates in research and development or clinical testing. At the same time, medical device naming and advertising regulations in mainland China must be complied with, and expressions such as "," must not appear.