Understanding Improved Antibody Penetration in Cancer Treatment

Co-administered antibody improves penetration of antibody–dye conjugate into human cancers with implications for antibody–drug conjugates

Guolan Lu, Naoki Nishio, and their team address a persistent problem: inadequate penetration of antibody-based cancer treatments into solid tumors. Though antibodies promise a more targeted attack on cancer, delivering them effectively remains a puzzle.

 

 

Current Obstacles: Penetration and Dosing Concerns

The potency of ADCs, which couple antibodies with cytotoxic agents, has necessitated lower dosing due to safety concerns. The downside is reduced tissue penetration, limiting their therapeutic effectiveness. As ADCs gain approval, fine-tuning dosing to maximize benefits and minimize harm becomes crucial.

 

Potential Solution: Co-administration Strategy

An intriguing strategy proposes co-administering the parent antibody with the ADC, aiming to enhance tissue penetration. Although promising in preclinical studies, its real-world application remains untested. The central question: can co-administration improve distribution in actual human tumors?

 

Key Findings: Using a Unique Imaging Tool

By leveraging a near-infrared fluorescence-labeled antibody, researchers tracked antibody distribution within tumors. Results were encouraging: co-administration with the parent antibody optimized intratumoral distribution of the antibody–dye conjugate. Critically, it did so without increasing uptake in healthy tissue, a potential sign of reduced side effects.

 

Conclusion: Implications for Future Cancer Therapies

Poor tissue penetration has curbed the potential of antibody-based treatments for years. This research suggests a promising direction: higher antibody doses, guided by advanced imaging, might enhance the therapeutic potency of ADCs, opening a new chapter in targeted cancer therapy.

 

 

 

References:

Lu, G., Nishio, N., van den Berg, N.S. et al. Co-administered antibody improves penetration of antibody–dye conjugate into human cancers with implications for antibody–drug conjugates. Nat Commun 11, 5667 (2020). https://doi.org/10.1038/s41467-020-19498-y.