000201434 001__ 201434
000201434 005__ 20181203023607.0
000201434 0247_ $$2doi$$a10.1158/2326-6066.Cir-14-0019-T
000201434 022__ $$a2326-6066
000201434 02470 $$2ISI$$a000340034200007
000201434 037__ $$aARTICLE
000201434 245__ $$aEnhancing Efficacy of Anticancer Vaccines by Targeted Delivery to Tumor-Draining Lymph Nodes
000201434 269__ $$a2014
000201434 260__ $$bAmer Assoc Cancer Research$$c2014$$aPhiladelphia
000201434 300__ $$a12
000201434 336__ $$aJournal Articles
000201434 520__ $$aThe 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. Nano-particle 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. (C) 2014 AACR.
000201434 700__ $$uEcole Polytech Fed Lausanne, Sch Life Sci, Inst Bioengn, Lausanne, Switzerland$$aJeanbart, Laura
000201434 700__ $$uEcole Polytech Fed Lausanne, Sch Life Sci, Inst Bioengn, Lausanne, Switzerland$$aBallester, Marie
000201434 700__ $$aDe Titta, Alexandre
000201434 700__ $$uEcole Polytech Fed Lausanne, Sch Life Sci, Inst Bioengn, Lausanne, Switzerland$$aCorthesy, Patricia
000201434 700__ $$aRomero, Pedro
000201434 700__ $$0240350$$g141360$$uEcole Polytech Fed Lausanne, Sch Life Sci, Inst Bioengn, Lausanne, Switzerland$$aHubbell, Jeffrey A.
000201434 700__ $$uEcole Polytech Fed Lausanne, Sch Life Sci, Inst Bioengn, Lausanne, Switzerland$$aSwartz, Melody A.$$g160091$$0242992
000201434 773__ $$j2$$tCancer Immunology Research$$k5$$q436-447
000201434 909C0 $$0252196$$pLMRP$$xU11032
000201434 909C0 $$xU11747$$0252115$$pLLCB
000201434 909CO $$particle$$ooai:infoscience.tind.io:201434
000201434 937__ $$aEPFL-ARTICLE-201434
000201434 973__ $$rREVIEWED$$sPUBLISHED$$aEPFL
000201434 980__ $$aARTICLE