Development and preclinical evaluation of cixutumumab drug conjugates in a model of insulin growth factor receptor I (IGF-1R) positive cancer.

ABSTRACT: Overexpression of insulin growth factor receptor type 1 (IGF-1R) is observed in many cancers. Antibody drug conjugates (ADCs) with PEGylated maytansine (PEG₆-DM1) show promise in vitro. We developed PEG₆-DM1 ADCs with low and high drug to antibody ratios (DAR) using an anti-IGF-1R antibody cixutumumab (IMC-A12). Conjugates with low (cixutumumab-PEG₆-DM1-Low) and high (cixutumumab-PEG₆-DM1-High) DAR as 3.4 and 7.2, respectively, were generated. QC was performed by UV spectrophotometry, HPLC, bioanalyzer, and biolayer-interferometry. We compared the in vitro binding and internalization rates of the ADCs in IGF-1R-positive MCF-7/Her18 cells. We radiolabeled the ADCs with ¹¹¹In and used microSPECT/CT imaging and ex vivo biodistribution to

SUBMITTER: Solomon VR 

PROVIDER: S-EPMC7596529 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature