Abstract 4576: Targeted human cytolytic fusion proteins: an update

Abstract

Abstract Targeted immunotherapeutics, such as antibody drug conjugates (ADCs) or immunotoxins (ITs) represent promising agents for treatment of cancer. Despite their encouraging performance in clinical trials, both ADCs and ITs suffer from disadvantages like stoichiometrically undefined chemical linkage of the cytotoxic payload and potential immunogenicity of bacteria- or plant-derived toxins in humans, respectively. Therefore, in contrast to depleting B cell epitopes from bacterial toxins, we designed a number of targeted recombinant cytolytic fusion proteins, replacing bacterial toxins like Pseudomonas exotoxin A by human enzymes like proteases, kinases, RNases or microtubuli-associated proteins. Binding and biological activities were shown in vitro, ex vivo and in different in vivo models. This presentation will summarize the latest results on the hCFPs generated and demonstrate the efficacy of treatment of CD64-, CSPG4-, and EpCAM-targeting constructs in direct comparison to the corresponding Pseudomonas exotoxin-based immunotoxins. The presentation will conclude with an outlook on future perspective and applications of the next generation of targeted fully human recombinant cytolytic fusion proteins. Citation Format: Stefan Barth. Targeted human cytolytic fusion proteins: an update [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4576. doi:10.1158/1538-7445.AM2017-4576