Abstract: The present disclosure relates to a novel antibody-drug conjugate (ADC) targeting claudin 18 isoform 2 (CLDN18.2), an active metabolite of the ADC, a method of producing the ADC, use of the ADC for the treatment and/or prevention of diseases, and use of the ADC for producing a drug for the treatment and/or prevention of diseases, more specifically hyperproliferative and/or angiogenic diseases, for example, cancer, and more particularly, to an antibody-drug conjugate including a novel antibody or antigen-binding fragment thereof that binds to CLDN18.2, and a pharmaceutical composition including the same.

Abstract: The present invention discloses CLDN18.2-targeting antibodies, bispecific antibodies and use thereof The CLDN18.2-targeting antibody is a single-domain heavy-chain antibody that has high affinity for tumor cells endogenously expressing CLDN18.2 and can induce high endocytic activity. The bispecific antibody can target CLDN18.2 and CD3 and retains the binding effect of an Fc to an FcRn; meanwhile, a mutant Fc is preferred so as to reduce the binding to an FcgR and thus the activation of non-specific T cells caused by the cross-linking of an FcgR. The CD3-terminus activity is optimized so that the release of common cytokines in CRS, such as IL6 and TNF? can be reduced.

Abstract: Provided are a CLDN18.2-targeting antibody or an antigen-binding fragment thereof, a preparation method therefor, and the use thereof. The antibody comprises a light chain variable region and/or a heavy chain variable region, and the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3. Compared with the prior art, the antibody has significant advantages in terms of binding affinity, ADCC, CDC, inhibitory effects on growth, endocytic activity, etc.