Создание и сравнител ьный анализ химерных антигенных рецепторов, специфичных к CD20

Abstract

Despite many advances in target therapies, survival of patients with rALL remains dismal, particularly among adults. Nonetheless, adoptive transfer of T-cells expressing chimeric antigen receptors (CARs) specific for the surface B cell molecule CD19 has been shown to be highly successful, as 50-90% of rALL patients receiving this therapy have achieved spectacular and durable remissions. This has inspired several research groups to develop CARs recognizing alternative B-cell targets, such as CD20, CD22, and BCMA, so as to use them in patients with other B-cell malignancies or help the patients that are unlikely to respond to CD19CAR T-cell therapy. Currently, there are two CD20-specific CARs in clinical trials. These CARs are based on the sequences of murine monoclonal antibodies Leu16 and 1F5 and use distinct hinge, transmembrane and signaling modules. Although both of these CARs appear to work, their side-by-side comparisons or structural optimization have never been performed in vitro or in vivo. The goal of our project was to design a CD20-specific CAR based on the human monoclonal antibody 2F2 (ofatumumab) and to compare this CAR to Leu16- and 1F5-based CARs in a unified context.