Nanoassemblies for the intracellular delivery of monoclonal antibodies in cancer therapy

  1. López Estévez, Ana María
Dirixida por:
  1. María José Alonso Fernández Director
  2. Dolores Torres López Director

Universidade de defensa: Universidade de Santiago de Compostela

Fecha de defensa: 06 de outubro de 2023

Tribunal:
  1. Maria Marlow Presidente/a
  2. Pablo Aguiar Fernández Secretario
  3. Carmen María Evora García Vogal

Tipo: Tese

Resumo

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.