On September 9, the R & D team of T>♥hoth Institutes (Nanjing) and Nan≥‌¥βjing RegeneCore ↓±↔Biotech Co.,Ltd cooperated with the team of Profeε∏ssor Gaojie Song of East China Nor✔>↓mal University to explore the structu≈×±γral basis for the action of bispec≈‌'ific nanobodies targeting IL-4↑♣≠Rα/IL-5. Some γ₽results were published in the fπ®amous academic periodical me✘ εdcomm (Qiu, et al., Structural insight into interleukin-4R&alph₹₩a; and interleukin-5 inhibition by nano'✔←bodies from a bispecific an☆¥¥€tibody,  09 September 2024）.This π®×study showed that the scre↑​ened nanobody Dab1 exhibited hig₹¶&Ωhly specific binding ability♥₽‌ and signal blocking  ‌®♠activity to human IL-4R&alp¶αha;.

Fig. Crystal structure of IL-4Rα in cπ≈₹↓omplex with dAb1 (left↓↓®♦) and comparison with the IL-4–IL-☆Ωδ♣4Rα (middle) or ♠>​→Dupilumab–IL-4R&al♦≈♣pha; (right).

Cytokines such as IL-4Rα and IL≥←-5 play important roles i£★n human immune regulation and type II inflammatiγ↓₽✔on. Regenecore used own nan®<₩obody platform to screen and co←$nstruct bispecific nanobodies targe↕•¥✔ting IL-4Rα and IL-5. The joint tβ↓•eam solved the complex structure of §₹β↓IL-4Rα and its correspond¶'ing monoclonal antibody byΩδ★ combining structural biology methods, and the≠∑←​ latter explained the molecular mechanism by whic<✘≈>h the antibody block‍‌ed the interaction b €₩≠etween IL-4Rα and its ligand: the aγ&ntibody mainly binds to  ‌$the key loop on IL-4R α through its own×♥ε hydrophobic pocket, wh"☆ich is also an important site for its™≈ → binding ligand. At the same ti✘εme, the team also used mo→±≈lecular modeling and mutant bioc•σhemical experiments to suggest the po≥←ssible binding site and inhibition mechan↔→∑ism of the nanobody c•✔☆orresponding to IL-5.

This work was supported by the N '™ational Natural Science Foundation of ∞×China, the basic resear ♦♠∏ch program of Science and Technology €÷π>Commission of Shanghai Municipa☆∞♦lity, and the thoth institutes for health pr₹∏$≠oject.

Original Article Link：♣©https://doi.org/10.1002/mco2.700