pH-sensitive Antibodies

Innovative therapeutic antibodies with unique pH-sensitive properties are emerging as a promising approach in oncology, offering enhanced specificity and reduced on-target  off-tumor effects. These antibodies are designed to be active only in the acidic tumor microenvironment (TME) for improved efficacy and safety profiles.

Advantages and Applications of pH-sensitive technology

pH-sensitive antibodies offer several significant advantages in therapeutic applications such as improvement of targeting and specificity, increased therapeutic efficacy and optimized pharmacokinetics properties:

  • Tumor selectivity and improved therapeutic index: exploits differences in pH between tumor and normal tissues
  • Reduced Off-tumor effects, minimizing binding to healthy tissues at physiological pH.

These innovative antibodies represent a significant advancement in cancer therapeutics, offering the potential for more precise and effective treatments across multiple oncology indications.

pH-Sensitive Antibody Discovery

Backed by Mabqi proprietary know-how and 1st generation fully human synthetic naive antibody library, our innovation team developed a next-generation synthetic pH-sensitive pHuscI2™ library based on optimized paratopes.

 

This approach allows for:

  • Preferential binding to cancer antigens under acidic tumor microenvironment conditions
  • Reduced binding to normal tissues at physiological pH
  • Potential for improved safety profiles and reduced toxicity.

 

Versatility in therapeutic antibody formats

The pH-sensitive antibody technology demonstrates remarkable adaptability to various pharmaceutical development formats:

 

  • Monoclonal Antibodies:
    mAbs with pH-sensitive binding properties are developed to enhance a therapeutic efficacy and reduce side effects. This particular characteristic can be leveraged to precisely target cells in acidic microenvironments, such as tumors.
  • Antibody-Drug Conjugates (ADCs):
    pH-sensitive antibodies can be incorporated into ADCs, potentially enhancing tumor-specific drug delivery and minimizing systemic toxicity.

 

Generating tumor-selective conditionally active immunotherapies: Antibody discovery campaign

Our antibody discovery team generates pH-sensitive antibodies for solid tumors in oncology:

 

  • pHuscI2™ designed library to generate pH-sensitive antibodies
  • AI-powered phage-yeast display selection process optimized for rapid identification of best pH- sensitive clones
  • Confirmation of pH-sensitive functionality: in vitro binding and kinetics
  • Additional functional assays such as internalization assays for ADC development, in vitro cytotoxicity on target expressing cells, fit-for-purpose assays