期刊
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
卷 152, 期 -, 页码 348-357出版社
ELSEVIER
DOI: 10.1016/j.ejpb.2020.05.026
关键词
Therapeutic vaccines; HPV-transformed pulmonary tumors; Toll-like and nod-like receptor agonists; Liposomal nanoparticles; Delivery system
资金
- Alsace contre le Cancer
- Centre National de la Recherche Scientifique (CNRS)
- University of Strasbourg
- Agence Nationale de la Recherche Program Investissements d'Avenir (Equipex) [I2MC/ANR-11-EQPX-022, LabEx Medalis/ANR-10-LABX-0034]
- french Ministere de l'Education Nationale, de la Recherche et de la Technologie
- La Ligue contre le Cancer [IP-SCG-JD-14779]
- french Fondation pour la Recherche Medicale
Liposomes are powerful tools for the optimization of peptides and adjuvant composition in cancer vaccines. Here, we take advantage of a liposomal platform versatility to develop three vaccine candidates associating a peptide from HA influenza virus protein as CD4 epitope, a peptide from HPV16 E7 oncoprotein as CD8 epitope and TLR4, TLR2/6 or NOD1 agonists as adjuvant. Liposomal vaccine containing MPLA (TLR4 liposomes), are the most effective treatment against the HPV-transformed orthotopic lung tumor mouse model, TC-1. This vaccine induces a potent Th1-oriented antitumor immunity, which leads to a significant reduction in tumor growth and a prolonged survival of mice, even when injected after tumor appearance. This efficacy is dependent on CD8(+) T cells. Subcutaneous injection of this treatment induces the migration of skin DCs to draining lymph nodes. Interestingly, TLR2/6 liposomes trigger a weaker Th1-immune response which is not sufficient for the induction of a prolonged antitumor activity. Although NOD1 liposome treatment results in the control of early tumor growth, it does not extend mice survival. Surprisingly, the antitumor activity of NOD1 vaccine is not associated with a specific adaptive immune response. This study shows that our modulable platform can be used for the strategical development of
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