A Novel Antibody-Toxin Conjugate to Treat Mantle Cell Lymphoma

In this study, we examined the anti-tumor effect of the antibody toxin conjugate (ADC) against activated matriptase positive mantle cell lymphoma cell lines (JeKo-1, Maver, Mino, and Z138). This ADC was cytotoxic to these cell lines with IC50s between 5 and 14 μg/mL. The ADC also showed a dose dependent anti-tumor effect on the JeKo-1 xenograft in mice without toxicity. Introduction Mantle Cell Lymphoma (MCL), represents 6- percent of all lymphoma cases, and currently the survival time is 4–5 years, shorter compared to other hematologic malignancies (2–4). MCL cells express CD20, aberrant expression of CD5, and due to a translocation t(11;14)(q13;q32), overexpression of cyclin-D1, encoded by the CCND1 gene located on chromosome 11, which mediates cell cycle progression through the G1 phase (5, 6). The currently used drugs to treat MCL patients include bortezomib, ibrutinib, rituximab, bendamustine, and combinations of these drugs. Matriptase, a glycoprotein (80–90 kDa), is a member of type II transmembrane serine proteases. It is synthesized as a latent single-chain structure and with many regulatory mechanisms and functions (7, 8), and is activated through an auto-activation step resulting in a disulfide-linked-two-chain structure. Following activation, matriptase is rapidly inactivated by its endogenous inhibitor HAI-1. This activated matriptase-HAI-1 complex remains present in most epithelial carcinomas and some B-cell malignancies ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research