Targeting antitumoral proteins to breast cancer by local administration of functional inclusion bodies

Abstract

Biofabrication; Cancer therapy; Functional amyloidsBiofabricación; Terapia contra el cáncer; Amiloides funcionalesBiofabricació; Teràpia contra el càncer; Amiloides funcionalsTwo structurally and functionally unrelated proteins, namely Omomyc and p31, are engineered as CD44-targeted inclusion bodies produced in recombinant bacteria. In this unusual particulate form, both types of protein materials selectively penetrate and kill CD44+ tumor cells in culture, and upon local administration, promote destruction of tumoral tissue in orthotropic mouse models of human breast cancer. These findings support the concept of bacterial inclusion bodies as versatile protein materials suitable for application in chronic diseases that, like cancer, can benefit from a local slow release of therapeutic proteins.This study has been supported by La Fundacio Marato TV3 and NanoCanTri (CIBER-BBN) to E.V. and I.A., and partially by ISCIII (PI15/00272 and PI1702242 co-founded by Fondo Europeo de Desarrollo Regional (FEDER), to E.V. and S.S., respectively), and Agencia Estatal de Investigacion (AEI) and FEDER (BIO2016-76063-R, AEI/FEDER, UE), AGAUR (2017SGR-229) and CIBER-BBN (VENOM4CANCER) granted to A.V. Protein production and DLS have been partially performed by the ICTS "NANBIOSIS," more specifically by the Protein Production Platform of CIBER-BBN/IBB () and the Biomaterial Processing and Nanostructuring Unit (), respectively. Biodistribution and immunohistochemistry assays were performed at the ICTS "NANBIOSIS," specifically by U20/FVPR (). L.S.-G. was supported by predoctoral fellowship from AGAUR (2018FI_B2_00051). L.S. was supported by the European Research Council (CoG #617473) and the Instituto de Salud Carlos III (FIS #PI16/01224). J.S.-F. was supported by an AECC post-doctoral fellowship. A.V. received an ICREA ACADEMIA awar