The invention discloses a
bispecific antibody targeting heterogeneous macrophages, and relates to the field of biological medicines. According to the present invention,
bevacizumab is adopted as a parent
antibody skeleton,
antibody arms targeting CD16 are arranged on the N end side,
antibody arms targeting CD163 are located on the C end side, knob
mutation (K322A and T366W) is introduced into the
heavy chain CH3 structural domain targeting CD16, three complementary hole mutations (T366S, L368A and Y407V) are introduced into the
heavy chain CH3 structural domain targeting CD163, and
cysteine residues are inserted into the S354 site of the knob chain and the Y349 site of the hole chain; variable regions (V regions) targeting CD16 and CD163 are connected in series through a (G4S) 3 flexible
linker and then fused with respective constant regions (C regions). The double-antibody architecture disclosed by the invention realizes collaborative optimization in
structural stability, double-
antigen binding specificity,
macrophage targeting and
functional activity, provides an efficient and safe novel candidate
drug for
targeted therapy of related diseases, and has important clinical transformation value and application prospect.