α-Galactosylceramide and peptide-based nano-vaccine synergistically induced a strong tumor suppressive effect in melanoma.
α-Galactosylceramide and peptide-based nano-vaccine synergistically induced a strong tumor suppressive effect in melanoma.
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DOI：
10.1016/j.actbio.2018.06.029
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发表时间：
2018-08
影响因子：
9.7
通讯作者：
F Florindo H
中科院分区：
文献类型：
--
作者：
Sainz V;Moura LIF;Peres C;Matos AI;Viana AS;Wagner AM;Vela Ramirez JE;S Barata T;Gaspar M;Brocchini S;Zloh M;Peppas NA;Satchi-Fainaro R;F Florindo H
α-半乳糖神经酰胺（GalCer）是一种糖脂，被广泛认为是自然杀伤T细胞（NKT）的激活剂，是一种有希望的抗癌佐剂，包括黑色素瘤。然而，迄今为止获得的临床结果有限。本研究评估了GalCer与主要组织相容性复合体（MHC） I类和MHC II类黑色素瘤相关肽抗原以及toll样受体（TLR）配体CpG和单磷酰脂质A （MPLA）之间的协同作用，我们打算在纳米颗粒（NP）共同递送后最大化它们之间的协同作用。这有望改善树突状细胞（dc）捕获GalCer并随后提交给NKT细胞，同时诱导抗肿瘤特异性t细胞介导的免疫。GalCer与黑色素瘤肽和TLR配体的结合成功地抑制了肿瘤的生长。这些动物的肿瘤体积比不含GalCer的NPs免疫小鼠的肿瘤体积小5倍。然而，当与抗原和TLR配体混合时，被包裹或以其可溶性形式存在的GalCer将肿瘤生长控制在相似的水平。这两组的T淋巴细胞向肿瘤的浸润均有改善，但只有负载galcer的纳米疫苗诱导了NKT和NK细胞的浸润。此外，这些动物的脾细胞分泌的IFN-γ和IL-4水平分别比用抗原和佐剂混合溶液处理的小鼠高至少1.5倍和2倍。总的来说，通过这种多价纳米疫苗联合递送NKT激动剂与TLR配体和黑色素瘤抗原，在B16F10黑色素瘤小鼠模型中显示出协同抗肿瘤免疫介导的功效。
α-Galactosylceramide (GalCer) is a glycolipid widely known as an activator of Natural killer T (NKT) cells, constituting a promising adjuvant against cancer, including melanoma. However, limited clinical outcomes have been obtained so far. This study evaluated the synergy between GalCer and major histocompatibility complex (MHC) class I and MHC class II melanoma-associated peptide antigens and the Toll-Like Receptor (TLR) ligands CpG and monophosphoryl lipid A (MPLA), which we intended to maximize following their co-delivery by a nanoparticle (NP). This is expected to improve GalCer capture by dendritic cells (DCs) and subsequent presentation to NKT cells, simultaneously inducing an anti-tumor specific T-cell mediated immunity. The combination of GalCer with melanoma peptides and TLR ligands successfully restrained tumor growth. The tumor volume in these animals was 5-fold lower than the ones presented by mice immunized with NPs not containing GalCer. However, tumor growth was controlled at similar levels by GalCer entrapped or in its soluble form, when mixed with antigens and TLR ligands. Those two groups showed an improved infiltration of T lymphocytes into the tumor, but only GalCer-loaded nano-vaccine induced a prominent and enhanced infiltration of NKT and NK cells. In addition, splenocytes of these animals secreted levels of IFN-γ and IL-4 at least 1.5-fold and 2-fold higher, respectively, than those treated with the mixture of antigens and adjuvants in solution. Overall, the combined delivery of the NKT agonist with TLR ligands and melanoma antigens via this multivalent nano-vaccine displayed a synergistic anti-tumor immune-mediated efficacy in B16F10 melanoma mouse model.
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DOI：
10.1158/1078-0432.ccr-10-3262
发表时间：
2011-06-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
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作者：
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影响因子：
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影响因子：
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DOI：
10.1006/bbrc.1998.9773
发表时间：
1998-12-09
影响因子：
3.1
作者：
Aurell, CA;Wistrom, AO
通讯作者：
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TLR4 对于树突状细胞激活和化学应激癌细胞释放的 DAMP 增强抗肿瘤 T 细胞反应至关重要
影响因子：
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作者：
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通讯作者：
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