Solutions for Antibody-Drug Conjugates (ADCs) Development

ADC targets cancer cell antigens through antibodies, delivering cytotoxic drugs directly into tumor cells via internalization, which significantly reduces side effects. The internalization efficiency directly impacts the amount of payload delivered, making it a key evaluation criterion in drug design, including antibody screening and linker optimization. Therefore, screening antibodies with high internalization efficiency is essential in the early stages of development.

To support ADC internalization research, we have developed a specialized Antibody Internalization Detection Reagent (Cat. No. IGG-PZF2001), featuring a pH-sensitive red fluorescent dye that labels the human IgG Fc region. The reagent forms a stable fluorescent complex that enables detection of antibody endocytosis within cells. It delivers enhanced fluorescence in acidic compartments with minimal background, supporting flow cytometry, cell imaging, and other cellular analysis techniques.

Schematic of antibody internalization detection reagent principle

The efficacy of antibody-drug conjugates (ADCs) is determined not only by the ability of their Fab fragments to bind tumor-associated antigens but also by the interaction between their Fc fragments and Fc receptors. Fc-mediated effector functions—such as antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antibody-dependent cellular phagocytosis (ADCP)—play a crucial role in the elimination or suppression of tumor cells.

Additionally, the affinity of the Fc fragment for the neonatal Fc receptor (FcRn) is a key predictor of an antibody’s half-life. Therefore, optimizing antibody structures and selecting candidates with ideal Fc receptor affinity are essential strategies in the development of therapeutic antibodies.

We offer a comprehensive collection of Fc receptor products, including FcRn, FcγR, and their commonly studied mutants. Leveraging our extensive protein product resources and activity analysis experience, we can also provide high-quality SPR & BLI affinity testing services upon receiving your sample. To support your research, we also supply all necessary high-quality Fc receptor proteins free of charge for these experiments.

In the development of ADCs, the linker structure impacts stability, homogeneity, cytotoxic potency, tolerability, and pharmacokinetics (PK). Therefore, selecting the appropriate linker is crucial for optimizing the therapeutic potential and safety of ADCs.

Linkers are typically classified as cleavable or non-cleavable based on their cleavage mechanism. Current ADCs research primarily focuses on cleavable linkers, with cathepsin-cleavable linkers being the most widely used and extensively studied. Additionally, several other linker-cleaving enzymes are under investigation.

For the screening and validation of linkers for ADCs, we have developed a series of proteases specialized in linker cleavage, encompassing Cathepsin B, Cathepsin L, Cathepsin S, MMP-2, MMP-7, MMP-9, β-glucuronidase, β-galactosidase.

ADCs have a more complex structure compared to traditional small molecule drugs and antibody drugs, resulting in higher drug heterogeneity, which makes its PK studies more complex. Analytes for ADCs typically encompass total antibodies (both conjugated and unconjugated with cytotoxic payloads, DAR≥0); conjugated antibodies (antibody conjugated to payload, DAR≥1), the antibody-conjugated drug, free drugs, and their analogs. The quantification of total antibodies and conjugated antibodies commonly employs ELISA (Enzyme-linked Immunosorbent Assay), while the analysis of antibody-conjugated drugs, free drugs, and their metabolites frequently involves LC-MS (Liquid Chromatograph Mass Spectrometer).

In order to tackle the challenges and complexities associated with the PK analysis of ADCs, we have introduced a comprehensive range of products and services tailored for PK research. These offerings encompass biotinylated proteins, streptavidin (SA) series products, anti-Payload antibodies, anti-idiotypic antibodies, anti-idiotypic antibodies development services, PK method development, validation and transfer, kit development services and more.