Abstract 5553: Anti-CD19-CD22 antibody drug conjugate to reduce tumor recurrence in B-cell hematologic cancers

Abstract With 1,279,000 new cases in 2020 and high incidence of relapse, hematologic cancers present significant opportunity for drug development. B-cell caners arise from various developmental stages of the B lymphocyte, and occur in several forms, including leukemia, lymphoma, and multiple myeloma. CD19 and CD22 are validated targets for B cell cancers, each with multiple drugs approved. However, single targeting therapies showed a poor median response likely due to loss of antigen expression upon treatment stress. CD19&CD22 dual targeting antibody drug conjugate can be a powerful killer of B-cell cancers, with more targeted patient populations due to the high expression of CD19, and good anti-tumor efficacy due to the high internalizing ability of CD22.To this end, we developed 7E11-13G9, which is a bispecific antibody designed for antibody-drug-conjugate for a larger market of B-cell hematological cancers.By the strong CD19 binding arm of 7E11 and the efficient CD22-mediated internalizing arm of 13G9, 7E11-13G9 BsAb kills more tumor cells with high potency and efficacy. In tumor cell killing assay, bispecific 7E11-13G9 showed significantly better anti-tumor efficacy than any of the benchmark antibodies, and even better than the combination of the anti-CD19 benchmark Loncastuximab with the anti-CD22 benchmark Inotuzumab. Significantly better anti-tumor effect and delayed tumor recurrence of CD19-CD22 bispecific compared with single target was demonstrated in Nalm6 acute lymphocyte leukemia model. 7E11-13G9 BsAb is stable and has good productivity in transient expression. Proof of concept study of antibody drug conjugate based on 7E11-13G9 was prepared, and showed great anti-tumor efficacy both in vitro and in vivo. Citation Format: Liang Du, Tingting Wan, Yi Jin, Jijun Yuan. Anti-CD19-CD22 antibody drug conjugate to reduce tumor recurrence in B-cell hematologic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5553.