bioRxiv Cancer Biology· YE, J., Zhu, X., Lu, H., Coppola, J., Zhang, D., Tian, Y., Yang, Z., Chung, S., Cui, L.-A., Zhi, J., Wen, L., Jeff Xi, J., Wilson, I. A., Jardine, J., Wu, P. ·· 23 hours agoPickScore66
Affinity Maturation Enables Dual Targeting of Cancer-Associated MUC1-Tn/STn and Drives Potent Tumor Control
In brief
The anti-MUC1-Tn antibody 5E5 was affinity-matured through structure-guided directed evolution and yeast surface display, yielding variants that recognize both MUC1-Tn and MUC1-STn with high affinity. Co-crystal structures show that HCDR3 residue 98 tunes glycoform preference: Tyr98 favors MUC1-Tn, His98 strengthens MUC1-STn binding, and both support high-affinity recognition of the two glycoforms.
Why it matters
Structures localize glycoform recognition differences to HCDR3 residue 98, offering a transferable engineering strategy for affinity maturation against intratumoral glycoform heterogeneity.
Source: bioRxiv Cancer Biology · biorxiv.org