pH-dependent Antibody Products: Accelerate Your Drug Discovery Process

Introduction to pH-dependent Antibody

The development of pH-dependent antibodies represents a significant leap forward in biotherapeutics. Traditional antibodies, while effective, are often subject to a buffering effect where a high concentration of the therapeutic can prevent the clearance of the very antigen it targets, reducing overall efficacy. The engineering antibodies with a pH-sensitive binding mechanism can circumvent this issue. These antibodies are designed to bind their targets in circulation and release them in the acidic endosome for degradation, thus increasing the therapeutic's efficiency and longevity. Also, pH-dependent antibodies are designed to be active only within the acidified tumor microenvironment. This improves their effectiveness and reduces harm to healthy tissues, making them a promising new tool for cancer therapy.

Fig. 1 pH-dependent antibody acts in the acidic tumor microenvironment (TME).^1,3

Features of pH-dependent Antibody

pH-dependent antibodies represent a major advance over traditional antibodies by fundamentally altering their interaction with the biological recycling machinery. This unique mechanism offers several distinct advantages.

• Enhanced Internalization and Downregulation: pH-dependent antibodies are designed to release their target once inside the acidic endosome. This ensures the antigen is routed for lysosomal degradation. This process, also known as antigen sink, leads to a more pronounced and durable reduction in the target protein's concentration.
• Increased Therapeutic Effects: The ability of pH-dependent antibodies to "hand off" their antigen for destruction means a single antibody molecule can perform multiple rounds of binding and clearance. This cyclical action amplifies the therapeutic effect, a lower required dose and a reduced frequency of administration.
• Superior Pharmacokinetics: The pH-dependent mechanism effectively uncouples the half-life of the antibody from that of its antigen. The antibody is efficiently recycled back to the bloodstream via the neonatal Fc receptor (FcRn) pathway after releasing its target. The half-life of antibody is extended and available to clear additional antigen molecules, leading to improved pharmacokinetics and pharmacodynamics.

Applications of pH-dependent Antibody

The unique properties of pH-dependent antibodies make them exceptionally valuable for a wide array of research and clinical applications, particularly in areas where conventional antibodies fall short.

Our pH-dependent Antibody Products

Creative Biolabs is a leader in engineering intelligent antibodies, and our pH-dependent antibody service is a core part of that expertise. We are uniquely equipped to handle the complexities of this technology with our proprietary platforms and rigorous processes.

Our pH-dependent antibody development platform allows for a streamlined, sequence-based approach to predict promising histidine mutations, circumventing the need for computationally intensive 3D structures that are often unavailable. This platform, combined with our proven combinatorial library generation and dual-pH screening methods, ensures we deliver highly effective candidates with superior properties. Our clients experience an average 40% increase in drug lead compound screening efficiency and a 30% reduction in protein expression costs.

Fig. 2 Generation of pH-dependent Antibody.^{2, 3}

Contact Us

At Creative Biolabs, our mission is to empower your innovation. Our team of experts is ready to discuss your specific project needs and demonstrate how our advanced pH-dependent Antibody services can provide you with a significant competitive advantage in the biopharmaceutical landscape. Contact us for your project!

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References

1. Smith, F. Donelson, et al. "Conditionally active, pH-sensitive immunoregulatory antibodies targeting VISTA and CTLA-4 lead an emerging class of cancer therapeutics." Antibodies 12.3 (2023): 55. https://doi.org/10.3390/antib12030055
2. Klaus, Tomasz, and Sameer Deshmukh. "pH-responsive antibodies for therapeutic applications." Journal of biomedical science 28.1 (2021): 11. https://doi.org/10.1186/s12929-021-00709-7
3. Distributed under Open Access license CC BY 4.0, without modification.

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