In a significant move to address the ‘undruggable’ targets in oncology and immunology, Creative Biolabs has announced the expansion of its advanced antibody engineering capabilities in drug development, such as antigen accumulation and on-target/off-tumor toxicity.
Traditional monoclonal antibodies (mAbs) often face a limitation: they bind to soluble antigens but can inadvertently increase the antigen’s half-life through FcRn recycling, leading to accumulation in the plasma.
Creative Biolabs’ eliminating antibody platform utilizes a “sweeping” mechanism that fundamentally changes how antigens are processed:
To improve the safety profile of potent biologics, Creative Biolabs highlights two synergistic technologies focused on the tumor microenvironment (TME):
1. Antibody Prodrugs: The Protease Switch
Many high-potential targets (e.g., EGFR, CD71) are discarded due to toxicity in healthy tissues. Creative Biolabs’ antibody prodrugs remain inactive in systemic circulation, masked by a peptide linker. They are only “switched on” when they encounter specific proteases overexpressed in the TME. This ensures the drug is potent only where it needs to be.
2. pH-Dependent Engineering
Complementing the prodrug approach, pH-dependent antibodies are engineered to exploit the acidic nature of the TME.
Successful antibody engineering requires rigorous validation. Creative Biolabs continues to support the research community with high-specificity proteolytic enzymes. These reagents are critical for analyzing antibody fragments (Fab, Fc) and characterizing post-translational modifications, ensuring that novel therapeutics meet strict quality control standards before entering clinical trials.
Q: Can eliminating antibody technology be applied to targets that are difficult to neutralize?
A: Yes. A key advantage of eliminating antibodies is their ability to remove antigens from circulation physically (“sweeping”), even if the antibody lacks direct in vitro neutralizing activity. This makes them ideal for multi-epitope antigens or toxins.
Q: How do antibody prodrugs minimize toxicity?
A: Antibody prodrugs utilize a “masking” technology. The active binding site is blocked by a peptide linker that can only be cleaved by proteases found specifically in the tumor microenvironment (e.g., MMPs), preventing the antibody from binding to healthy tissues.
Q: What information is needed to start a pH-dependent antibody project?
A: To initiate a project, Creative Biolabs typically requires the antibody sequence or a pre-existing binder, along with well-characterized antigen data. Structural data can further accelerate the design process.
Learn more about pH-dependent antibodies
