Trp2 peptide vaccine adjuvanted with (R)-DOTAP inhibits tumor growth in an advanced melanoma model.
Trp2 peptide vaccine adjuvanted with (R)-DOTAP inhibits tumor growth in an advanced melanoma model.
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DOI：
10.1021/mp200350n
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发表时间：
2012-02-06
影响因子：
4.9
通讯作者：
Huang L
中科院分区：
文献类型：
--
作者：
Vasievich EA;Ramishetti S;Zhang Y;Huang L
以前我们已经显示阳离子脂质（R）-DOTAP作为DOTAP外消旋混合物的免疫活性对映体，在外源性抗原模型（鼠宫颈癌模型）中启动完全肿瘤消退。在此，我们研究了（R）-DOTAP在侵袭性鼠实体瘤黑色素瘤模型中作为递送内源性抗原的有效佐剂的用途。（R）-DOTAP/Trp 2肽复合物显示随着肽浓度的增加而减小的尺寸和电荷，在最高浓度下呈棒状。颗粒在4°C下稳定2周。与5和25 nmol的较低剂量相比，75 nmol的Trp 2（在（R）-DOTAP中配制）的剂量能够显示统计学上显著的肿瘤生长延迟，所述较低剂量与未处理的肿瘤没有不同。（R）-DOTAP/Trp 2（75 nmol）处理的小鼠在用Trp 2再刺激后也显示增加的T细胞IFN-γ分泌以及体内CTL活性。该疫苗接种组还显示出功能活性肿瘤浸润淋巴细胞的最高群体，由用Trp 2再刺激后的IFN-γ分泌指示。因此，（R）-DOTAP显示出作为佐剂破坏耐受性的能力。其增强其他肿瘤相关抗原免疫原性的活性有待进一步研究。
Previously we have shown cationic lipid (R)-DOTAP as the immunologically active enantiomer of the DOTAP racemic mixture, initiating complete tumor regression in an exogenous antigen model (murine cervical cancer model). Here, we investigate the use of (R)-DOTAP as an efficacious adjuvant delivering an endogenous antigen in an aggressive murine solid tumor melanoma model. (R)-DOTAP/Trp2 peptide complexes showed decreasing size and charge with increasing peptide concentration, taking a rod-shape at highest concentrations. The particles were stable for at 2 weeks at 4°C. A dose of 75nmol Trp2 (formulated in (R)-DOTAP) was able to show statistically significant tumor growth delay compared to lower doses of 5 and 25nmol which were no different than untreated tumors. (R)-DOTAP/Trp2 (75nmol) treated mice also showed increased T cell IFN-γ secretion after restimulation with Trp2, as well as CTL activity in vivo. This vaccination group also showed the highest population of functionally active tumor-infiltrating lymphocytes, indicated by IFN-γ secretion after restimulation with Trp2. Thus, (R)-DOTAP has shown the ability to break tolerance as an adjuvant. Its activity to enhance immunogenicity of other tumor associated antigens should be studied further.
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影响因子：
7.4
作者：
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