Titre
Enhancing efficacy of anticancer vaccines by targeted delivery to tumor-draining lymph nodes.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Jeanbart, L.
Auteure/Auteur
Ballester, M.
Auteure/Auteur
de Titta, A.
Auteure/Auteur
Corthésy, P.
Auteure/Auteur
Romero, P.
Auteure/Auteur
Hubbell, J.A.
Auteure/Auteur
Swartz, M.A.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
2326-6074
Statut éditorial
Publié
Date de publication
2014
Volume
2
Numéro
5
Première page
436
Dernière page/numéro d’article
447
Peer-reviewed
Oui
Langue
anglais
Résumé
The sentinel or tumor-draining lymph node (tdLN) serves as a metastatic niche for many solid tumors and is altered via tumor-derived factors that support tumor progression and metastasis. tdLNs are often removed surgically, and therapeutic vaccines against tumor antigens are typically administered systemically or in non-tumor-associated sites. Although the tdLN is immune-suppressed, it is also antigen experienced through drainage of tumor-associated antigens (TAA), so we asked whether therapeutic vaccines targeting the tdLN would be more or less effective than those targeting the non-tdLN. Using LN-targeting nanoparticle (NP)-conjugate vaccines consisting of TAA-NP and CpG-NP, we compared delivery to the tdLN versus non-tdLN in two different cancer models, E.G7-OVA lymphoma (expressing the nonendogenous TAA ovalbumin) and B16-F10 melanoma. Surprisingly, despite the immune-suppressed state of the tdLN, tdLN-targeting vaccination induced substantially stronger cytotoxic CD8+ T-cell responses, both locally and systemically, than non-tdLN-targeting vaccination, leading to enhanced tumor regression and host survival. This improved tumor regression correlated with a shift in the tumor-infiltrating leukocyte repertoire toward a less suppressive and more immunogenic balance. Nanoparticle coupling of adjuvant and antigen was required for effective tdLN targeting, as nanoparticle coupling dramatically increased the delivery of antigen and adjuvant to LN-resident antigen-presenting cells, thereby increasing therapeutic efficacy. This work highlights the tdLN as a target for cancer immunotherapy and shows how its antigen-experienced but immune-suppressed state can be reprogrammed with a targeted vaccine yielding antitumor immunity.
PID Serval
serval:BIB_4DFED4270DC4
PMID
Open Access
Oui
Date de création
2014-09-29T10:33:01.366Z
Date de création dans IRIS
2025-05-20T19:50:35Z