T cell-redirecting antibody for treatment of solid tumors via targeting mesothelin.

ABSTRACT: T cell engaging bispecific antibodies (TCBs) have recently become significant in cancer treatment. In this study we developed MSLN490, a novel TCB designed to target mesothelin (MSLN), a glycosylphosphatidylinositol (GPI)-linked glycoprotein highly expressed in various cancers, and evaluated its efficacy against solid tumors. CDR walking and phage display techniques were used to improve affinity of the parental antibody M912, resulting in a pool of antibodies with different affinities to MSLN. From this pool, various bispecific antibodies (BsAbs) were assembled. Notably, MSLN490 with its IgG-[L]-scFv structure displayed remarkable anti-tumor activity against MSLN-expressing tumors (EC₅₀: 0.16 pM in HT-29-hMSLN cells). Furthermore, MSLN490 remained effective even in the presence

SUBMITTER: Liu JJ 

PROVIDER: S-EPMC11420237 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature