Nanoassemblies for the intracellular delivery of monoclonal antibodies in cancer therapy

Abstract

Mutations in the Kirsten Rat Sarcoma Virus (KRAS) oncoprotein are particularly relevant therapeutic targets in lung cancer, among others. Although one KRAS mutation has been addressed, KRAS is still considered an undruggable target. In this scenario, monoclonal antibodies (mAbs) have emerged as the main alternative to achieve a positive efficacy/toxicity balance while blocking intracellular oncoproteins. Hence, we have developed novel nanoassemblies (HANAs) for the intracellular delivery of mAbs and functionalized or not with the tumor penetrating peptide tLyP1. HANAs were evaluated according to i) the capacity to load mAbs, ii) the ability to modify the biodistribution profile of the mAb, and iii) the performance in terms of activity and target engagement towards the KRASG12V oncoprotein.