Preclinical optimization of Ly6E-targeted ADCs for increased durability and efficacy of anti-tumor response.

ABSTRACT: Early success with brentuximab vedotin in treating classical Hodgkin lymphoma spurred an influx of at least 20 monomethyl auristatin E (MMAE) antibody-drug conjugates (ADCs) into clinical trials. While three MMAE-ADCs have been approved, most of these conjugates are no longer being investigated in clinical trials. Some auristatin conjugates show limited or no efficacy at tolerated doses, but even for drugs driving initial remissions, tumor regrowth and metastasis often rapidly occur. Here we describe the development of second-generation therapeutic ADCs targeting Lymphocyte antigen 6E (Ly6E) where the tubulin polymerization inhibitor MMAE (Compound 1) is replaced with DNA-damaging agents intended to drive increased durability of response. Comparison of a seco-cyclopropyl benz

SUBMITTER: Dela Cruz Chuh J 

PROVIDER: S-EPMC7784788 | biostudies-literature | 2021 Jan-Dec

REPOSITORIES: biostudies-literature