pH-dependent Antibody-Drug Conjugate (ADC) Products

Introduction of pH-dependent Antibody–Drug Conjugates (ADCs)

The pH-dependent Antibody–Drug Conjugate (ADC) is a promising advancement in oncology that addresses the limitations of conventional ADCs, such as systemic toxicity and a narrow therapeutic window. By engineering the antibody component to bind its target in a pH-dependent manner, these ADCs are designed to be active primarily within the acidic tumor microenvironment (TME). This approach can significantly improve tumor selectivity, reduce off-target side effects, and enable the treatment of a broader patient population, including those with lower target antigen expression levels.

Fig.1 The mechanism of action of Antibody-Drug Conjugates (ADCs).¹

Features of pH-dependent Antibody component of ADCs

pH-dependent antibodies are meticulously engineered to exploit the physiological pH gradient between normal tissue and the tumor microenvironment. This targeted approach results in several key features and advantages over conventional antibodies.

• Enhanced Internalization and Downregulation: pH-dependent antibodies are designed to release their antigen in the acidic endosome (pH ~5.5), which promotes greater internalization and a longer duration of action. This mechanism can lead to a significant increase in payload accumulation within tumor cells, with one study showing a fourfold higher net internalization compared to a non-engineered parent ADC. Confocal microscopy has also shown increased accumulation in lysosomes and less colocalization with recycling endosomes for pH-dependent variants, further supporting this mechanism.
• Overcoming Resistance Mechanisms: Tumor heterogeneity, particularly in antigen expression, can lead to resistance to single-target ADCs. By maximizing payload delivery and leveraging the bystander effect, pH-dependent ADCs can kill not only the high-expressing cells but also neighboring, low-expressing tumor cells. In addition, some conditional activation strategies, like probody-drug conjugates, use TME-specific factors like proteases or acidity to unmask the antibody, enabling it to bind to targets that are also expressed on healthy tissue.
• Improving Pharmacokinetics: For targets that are highly expressed on both tumor cells and normal tissues, conventional ADCs can be rapidly cleared from the circulation through target-mediated drug disposition (TMDD). pH-dependent antibodies, however, can be engineered to release their antigen in the acidic endosomes of normal cells and be recycled back to circulation via the FcRn pathway, leading to a longer serum half-life and greater drug exposure in tumors.

Production of pH-dependent Antibody Designed for Antibody–Drug Conjugates

Creative Biolabs offers a comprehensive, end-to-end service for the development and production of pH-dependent antibodies for your ADC projects. Our streamlined process is designed to deliver high-quality, customized therapeutic candidates efficiently.

Fig. 2 The workflow of pH-dependent antibody production.

Our pH-dependent Antibody products for Antibody–Drug Conjugate

Creative Biolabs is committed to accelerating your oncology drug discovery efforts with our next-generation ADC technologies. Our innovative pH-dependent antibody service delivers a tangible and measurable advantage for your ADC development. Our proprietary engineering platform focuses on rational design and rigorous validation, providing you with best-in-class pH-dependent antibody candidates.

• Superior Tumor Selectivity: Our pH-dependent antibodies bind selectively and robustly to the acidic tumor microenvironment, minimizing binding to healthy tissues at neutral pH. This drastically reduces "on-target, off-tumor" toxicity, a major limitation of conventional ADCs.
• Enhanced Therapeutic Index: By minimizing systemic toxicity and improving tumor-specific payload delivery, the pH-dependent antibody-drug conjugates expand the therapeutic window, allowing for higher, more effective dosing.
• Expanded Subject Population: Our ADCs have demonstrated efficacy in tumor models with low to moderate target antigen expression, broadening the subject population that can be treated successfully.

For more information and to discuss how our pH-dependent ADCs can benefit your specific project, please contact us. We are ready to answer your questions and help you design a superior therapeutic candidate.

FAQs

Reference

1. Long, Rou, et al. "Antibody-drug conjugates in cancer therapy: applications and future advances." Frontiers in Immunology 16 (2025): 1516419. Distributed under Open Access license CC BY 4.0, without modification. https://doi.org/10.3389/fimmu.2025.1516419

Our customer service representatives are available 24 hours a day, from Monday to Sunday. Contact Us

Can't find the products you're looking for? Try to filter in the left sidebar.Filter By Tag

For Research Use Only. Not For Clinical Use.