TY - JOUR
T1 - Liposomes as tunable platform to decipher the antitumor immune response triggered by TLR and NLR agonists
AU - Jacoberger-Foissac, Célia
AU - Saliba, Hanadi
AU - Wantz, May
AU - Seguin, Cendrine
AU - Flacher, Vincent
AU - Frisch, Benoît
AU - Heurtault, Béatrice
AU - Fournel, Sylvie
N1 - Funding Information:
This work was supported by “Alsace contre le Cancer”, the Centre National de la Recherche Scientifique (CNRS), the University of Strasbourg and the Agence Nationale de la Recherche Program “Investissements d'Avenir” (Equipex I2MC/ANR-11-EQPX-022 and LabEx Medalis/ANR-10-LABX-0034). Célia Jacoberger-Foissac was a recipient of a PhD grant from the french Ministère de l'Education Nationale, de la Recherche et de la Technologie, and from “La Ligue contre le Cancer” (grant number IP-SCG-JD-14779). Hanadi Saliba was funded by the french « Fondation pour la Recherche Médicale ».
Funding Information:
This work was supported by ?Alsace contre le Cancer?, the Centre National de la Recherche Scientifique (CNRS), the University of Strasbourg and the Agence Nationale de la Recherche Program ?Investissements d'Avenir? (Equipex I2MC/ANR-11-EQPX-022 and LabEx Medalis/ANR-10-LABX-0034). C?lia Jacoberger-Foissac was a recipient of a PhD grant from the french Minist?re de l'Education Nationale, de la Recherche et de la Technologie, and from ?La Ligue contre le Cancer? (grant number IP-SCG-JD-14779). Hanadi Saliba was funded by the french ? Fondation pour la Recherche M?dicale ?.
Publisher Copyright:
© 2020
PY - 2020/7
Y1 - 2020/7
N2 - 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 vaccines.
AB - 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 vaccines.
KW - Delivery system
KW - HPV-transformed pulmonary tumors
KW - Liposomal nanoparticles
KW - Therapeutic vaccines
KW - Toll-like and nod-like receptor agonists
UR - http://www.scopus.com/inward/record.url?scp=85085970778&partnerID=8YFLogxK
U2 - 10.1016/j.ejpb.2020.05.026
DO - 10.1016/j.ejpb.2020.05.026
M3 - Article
C2 - 32479782
AN - SCOPUS:85085970778
SN - 0939-6411
VL - 152
SP - 348
EP - 357
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
ER -