Development of α-Gal-Antibody Conjugates to Increase Immune Response by Recruiting Natural Antibodies.
Julinton SianturiYoshiyuki ManabeHao-Sheng LiLi-Ting ChiuTsung-Che ChangKento TokunagaKazuya KabayamaMasahiro TanemuraShinji TakamatsuEiji MiyoshiShang-Cheng HungKoichi FukasePublished in: Angewandte Chemie (International ed. in English) (2019)
Cancer treatment with antibodies (Abs) is one of the most successful therapeutic strategies for obtaining high selectivity. In this study, α-gal-Ab conjugates were developed that dramatically increased cellular cytotoxicity by recruiting natural Abs through the interaction between α-gal and anti-gal Abs. The potency of the α-gal-Ab conjugates depended on the amount of α-gal conjugated to the antibody: the larger the amount of α-gal introduced, the higher the level of cytotoxicity observed. The conjugation of antibodies with an α-gal dendrimer allowed the introduction of large amounts of α-gal to the Ab, without loss of affinity for the target cell. The method described here will enable the re-development of Abs to improve their potency.