Protein-based therapeutic killing for cancer therapies

Altres ajuts: CIBER-BBN (project NANOPROTHER) to A.V.; the Marató de TV3 foundation (TV32013-3930); CIBER-BBN (NanoMets 3) to R.M. in support of our research on cell-targeted antitumor drugs. N.S. by a predoctoral fellowship from the Gobierno de Navarra, R.D.O. by an overseas predoctoral fellowship from Conacyt (Gobierno de Méjico, 2016), U.U. received a Sara Borrell postdoctoral fellowship from ISCIII, and A.V. an Institución Catalana de Investigación y Estudios Avanzados (ICREA) ACADEMIA award.The treatment of some high-incidence human diseases is based on therapeutic cell killing. In cancer this is mainly achieved by chemical drugs that are systemically administered to reach effective toxic doses. As an innovative alternative, cytotoxic proteins identified in nature can be adapted as precise therapeutic agents. For example, individual toxins and venom components, proapoptotic factors, and antimicrobial peptides from bacteria, animals, plants, and humans have been engineered as highly potent drugs. In addition to the intrinsic cytotoxic activities of these constructs, their biological fabrication by DNA recombination allows the recruitment, in single pharmacological entities, of diverse functions of clinical interest such as specific cell-surface receptor binding, self-activation, and self-assembling as nanoparticulate materials, with wide applicability in cell-targeted oncotherapy and theragnosis