In conclusion, in this study, we described an optimized antibody, deglyco C1 IgG, that targets CLEC14a‐CTLD and demonstrated that targeting of CLEC14a‐CTLD may be an effective strategy for suppressing CLEC14a‐mediated VEGF‐dependent and tumor angiogenesis, which is closely associated with pathological angiogenesis. Here, CLEC14A is linked to neoplasm.