pH-sensitive antibodies: an approach to generate new tools for therapeutic precision
Information
The concept of dual-function antibodies has garnered significant attention in recent years. A particular class of such antibodies is pH-sensitive antibodies:
• pH-sensitive (bind 7.4, release 6.0) antibodies can neutralize soluble targets present in the extracellular environment by binding them at physiological pH, neutralizing the harmful effects of these targets and, upon cellular uptake, releasing the bound antigens in the acidic environment of the lysozyme, and to the degradative pathway. This process contributes to target clearance within the body and recycling of the antibody after detachment from the target in the lysozyme.
• A different class of pH-sensitive antibodies (bind pH 6.0, release 7.4) can selectively bind their targets at acidic pH, characteristic of the tumor microenvironment. As a result, binding outside the tumor microenvironment is diminished at physiological pH, allowingthese pH-dependent antibodies to target a broader range of tumor markers, including those not exclusively associated with tumor cells.
• Both classes of antibodies hold promise for clinical applications.
• In this presentation we show how it is possible to confer pH-sensitivity to a pre-selected antibodies that showed similar binding activity at different pHs and how it is possible to directly select pH-sensitive antibodies from recombinant antibody libraries.
