A proteomic approach for characterizing trastuzumab-emtansine modified for nuclear directed localization that enhances cytotoxicity identifies regulatory nuclear transport receptor.

ABSTRACT: We used the approved antibody-drug conjugate trastuzumab-emtansine and the HER2+ cell line SKBR3. We also used a novel technology termed cell accumulator (Accum) that enables mAbs to escape endosome entrapment and localize to the cell nucleus without abrogating antibody affinity or specificity to target antigens. Accum harbors a well-known nuclear localization signal (NLS) sequence recognized by the classic nuclear transportation receptor (NTR) complex alpha-importin/importin-beta. Accum-modification of T-DM1 resulted in a significant increase in cytotoxic potency. We sought to understand the mechanisms through which Accum-T-DM1 localized to the nucleus and increased tumor cell killing effectiveness.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Vincent Lacasse  

LAB HEAD: Jeffrey Victor Leyton

PROVIDER: PXD014786 | Pride | 2021-09-08

REPOSITORIES: Pride