Intratumor adoptive transfer of il-12 MRNA transiently engineered antitumor CD8+ T cells

• Autores: Iñaki Etxeberria Uriz
• Directores de la Tesis: Ignacio Melero Bermejo (dir. tes.)
• Lectura: En la Universidad de Navarra ( España ) en 2020
• Idioma: español
• Tribunal Calificador de la Tesis: Sandra Hervás Stubbs (presid.), Fernando Pastor Rodríguez (secret.), Alena Gros Vidal (voc.), David Escors (voc.), Francisco de Asís Palazón García (voc.)
• Programa de doctorado: Programa de Doctorado en Investigación Biomédica por la Universidad de Navarra
• Materias:
  • Ciencias de la vida
    • Biología celular
    • Inmunología
• Texto completo no disponible (Saber más ...)
• Resumen

  • Retroviral gene transfer of interleukin-12 (IL-12) into T cells markedly enhances antitumor efficacy upon adoptive transfer but has clinically shown unacceptable severe side effects. To overcome the toxicity, we engineered tumor-specific CD8+ T cells to transiently express IL-12. Engineered T cells injected intratumorally, but not intravenously, led to complete rejections not only of the injected lesion but also of distant concomitant tumors. Efficacy was further enhanced by co-injection with agonist anti-CD137 mAb or by transient co-expression of CD137 ligand. This treatment induced epitope spreading of the endogenous CD8+ T cell immune response in a manner dependent on cDC1 dendritic cells. Mouse and human tumor-infiltrating T lymphocyte cultures can be transiently IL-12 engineered to attain marked immunotherapeutic effects.