How Non-Fucosylated Antibodies Work Better in Cancer Treatment
Author Information
Author(s): Iida Shigeru, Kuni-Kamochi Reiko, Mori Katsuhiro, Misaka Hirofumi, Inoue Miho, Okazaki Akira, Shitara Kenya, Satoh Mitsuo
Primary Institution: Tokyo Research Laboratories, Kyowa Hakko Kogyo Co, Ltd
Hypothesis
What mechanisms allow non-fucosylated therapeutic antibodies to achieve higher antibody-dependent cellular cytotoxicity (ADCC) in human blood compared to fucosylated antibodies?
Conclusion
Removing fucosylated components from antibody therapeutics significantly enhances their ADCC efficacy in human blood through two main mechanisms.
Supporting Evidence
- Non-fucosylated anti-CD20 antibodies showed over 100-fold greater B-cell depletion activity compared to fucosylated ones.
- The binding of fucosylated antibodies to NK cells was almost abolished in the presence of human plasma.
- Non-fucosylated antibodies maintained high binding activity to NK cells even in the presence of plasma IgG.
Takeaway
Non-fucosylated antibodies are better at killing cancer cells because they can work around the body's defenses that usually block them.
Methodology
The study used a human ex vivo B-cell depletion assay to compare the binding and efficacy of non-fucosylated and fucosylated anti-CD20 antibodies.
Limitations
The study primarily focused on a limited number of healthy donors and may not fully represent diverse patient populations.
Participant Demographics
12 healthy volunteers (5 women and 7 men, aged 20 to 57 years)
Digital Object Identifier (DOI)
Want to read the original?
Access the complete publication on the publisher's website