The application discloses a method for modifying pH sensitivity of an
antibody based on
yeast display. A degenerate codon VAM (coding H, E, D, K, N, Q) is used to construct a
yeast display
library for at least two region combinations in LCDR1, HCDR1 and HCDR3, and 1-2 mutations are introduced into each CDR region, taking the
antibody to be modified as a template. The
library is transformed into
Saccharomyces cerevisiae EBY100 to induce expression, and fast dissociation clones are enriched through four rounds of
flow sorting (including pH 7.4 binding, pH 6.0 non-binding and'saturated binding-acid dissociation-neutral re-binding' screening). The obtained
antibody has a KD ratio at pH 5.8 to pH 7.4 of up to 674.46, an expression amount of up to 263.3 mg / L, excellent physicochemical properties, and can enhance the
curative effect of antibody conjugated drugs and improve the
therapeutic index.