Antibody targeting CLDN18.2, bispecific antibody and application thereof

The invention discloses an antibody targeting CLDN18.2, a bispecific antibody and an application of the bispecific antibody. The antibody for targeting the CLDN18.2 is a single-domain heavy-chain antibody, has relatively strong affinity to tumor cells for endogenous expression of the CLDN18.2, and can induce relatively strong endocytosis activity; the bispecific antibody can target CLDN18.2 and CD3, the binding effect of Fc and FcRn is reserved, meanwhile, mutated Fc is preferably selected to reduce binding with FcgR, and therefore non-specific T cell activation caused by the cross-linking effect of FcgR can be reduced; the activity of the CD3 terminal is optimized, so that the release of common cytokines such as IL6 and TNF alpha in the CRS can be reduced. 本发明公开了一种靶向CLDN18.2的抗体、双特异性抗体及其应用。所述靶向CLDN18.2的抗体为单域重链抗体，对内源性表达CLDN18.2的肿瘤细胞具有较强的亲和力，且可诱导较强的内吞活性；所述双特异性抗体可靶向CLDN18.2和CD3，保留了Fc与FcRn的结合作用，同时优选突变的Fc以降低与FcgR的结合，从而可降低因FcgR的交联作用而引起的非特异性T细胞活化；优化了CD3端的活性，从而可降低CRS中常见的细胞因子例如IL6及TNFα释放。