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Harnessing MerTK agonism for targeted therapeutics
Vivekananda Kedage1, Diego Ellerman2, Yongmei Chen3
1Department of Molecular Oncology, Genentech, South San Francisco, CA, USA.
This study introduces a novel bispecific antibody strategy to utilize MerTK for targeted cellular clearance. This method avoids the proinflammatory cytokine release often seen with Fcγ receptor engagement, offering a new therapeutic avenue.
Area of Science:
- Immunology
- Therapeutic antibody development
Background:
- Phagocytosis is crucial for homeostasis and disease.
- Fcγ receptor-mediated phagocytosis is a key mechanism in antibody therapies.
- MerTK-mediated phagocytosis offers an immunologically silent clearance pathway.
Purpose of the Study:
- To develop a bispecific antibody approach for MerTK-mediated targeted clearance.
- To demonstrate that MerTK engagement can achieve clearance without inducing proinflammatory cytokines.
- To showcase the versatility of this approach for targeting different entities.
Main Methods:
- Design and generation of bispecific antibodies.
- Utilizing bispecific antibodies to target MerTK.
- Evaluating the clearance of targeted cells or aggregates.
- Assessing cytokine release profiles.
Main Results:
- Successfully generated bispecific antibodies capable of engaging MerTK.
- Demonstrated targeted clearance of B cells and amyloid beta aggregates.
- Confirmed the absence of significant proinflammatory cytokine release compared to Fcγ receptor engagement.
Conclusions:
- Bispecific antibodies can effectively harness MerTK for targeted, immunologically silent clearance.
- This approach offers a promising alternative to Fcγ receptor-based therapies.
- The strategy is versatile and applicable to various targets like B cells and amyloid aggregates.
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