Complete regression and systemic protective immune responses obtained in B16 melanomas after treatment with LTX-315.
Complete regression and systemic protective immune responses obtained in B16 melanomas after treatment with LTX-315.
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DOI：
10.1007/s00262-014-1540-0
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发表时间：
2014-06
影响因子：
5.8
通讯作者：
Sveinbjornsson, Baldur
中科院分区：
文献类型：
--
作者：
Camilio, Ketil Andre;Berge, Gerd;Ravuri, Chandra Sekhar;Rekdal, Oystein;Sveinbjornsson, Baldur
恶性黑色素瘤是最具侵略性和最致命的形式的皮肤癌，由于其高度转移的潜力，这需要新的和改进的疗法。阳离子抗菌肽（cationicantimicrobial peptides，CAPs）是天然存在于大多数物种中的分子，在抵抗病原体的第一道防线中发挥着重要作用，其中一些CAPs已显示出作为新型抗癌药物的潜力。对CAP牛乳铁蛋白的构效关系研究使我们能够从头设计短的化学修饰的裂解性抗癌肽。在本研究中，我们研究了LTX-315对同基因小鼠皮内建立的B16黑色素瘤的体内抗肿瘤作用。肿瘤内施用LTX-315导致肿瘤坏死和免疫细胞浸润到肿瘤实质中，随后在大多数动物中肿瘤完全消退。LTX-315在体外诱导了高迁移率族蛋白-1蛋白等炎症相关分子模式分子的释放，随后在体内上调了白细胞介素（IL）1β、IL 6和IL 18等促炎细胞因子。通过LTX-315治疗治愈的动物被保护免受皮内和静脉内活B16肿瘤细胞的再攻击。总之，我们的数据表明，用LTX-315进行肿瘤内治疗可以提供局部肿瘤控制，随后是保护性免疫应答，并且具有作为新的免疫抑制剂的潜力。本文的在线版本（doi：10.1007/s 00262 -014-1540-0）包含补充材料，可供授权用户使用。
Malignant melanoma is the most aggressive and deadliest form of skin cancer due to its highly metastatic potential, which calls for new and improved therapies. Cationic antimicrobial peptides (CAPs) are naturally occurring molecules found in most species, in which they play a significant role in the first line of defense against pathogens, and several CAPs have shown promising potential as novel anticancer agents. Structure–activity relationship studies on the CAP bovine lactoferricin allowed us to de novo design short chemically modified lytic anticancer peptides. In the present study, we investigated the in vivo antitumor effects of LTX-315 against intradermally established B16 melanomas in syngeneic mice. Intratumoral administration of LTX-315 resulted in tumor necrosis and the infiltration of immune cells into the tumor parenchyma followed by complete regression of the tumor in the majority of the animals. LTX-315 induced the release of danger-associated molecular pattern molecules such as the high mobility group box-1 protein in vitro and the subsequent upregulation of proinflammatory cytokines such as interleukin (IL) 1β, IL6 and IL18 in vivo. Animals cured by LTX-315 treatment were protected against a re-challenge with live B16 tumor cells both intradermally and intravenously. Together, our data indicate that intratumoral treatment with LTX-315 can provide local tumor control followed by protective immune responses and has potential as a new immunotherapeutic agent. The online version of this article (doi:10.1007/s00262-014-1540-0) contains supplementary material, which is available to authorized users.
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影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
3.8
作者：
Fadnes B;Uhlin-Hansen L;Lindin I;Rekdal Ø
通讯作者：
Rekdal Ø
影响因子：
2.8
作者：
Chaves, F;Teixeira, CFP;Gutiérrez, JM
通讯作者：
Gutiérrez, JM
影响因子：
5.8
作者：
Berge, Gerd;Eliassen, Liv Tone;Rekdal, Oystein
通讯作者：
Rekdal, Oystein
影响因子：
4.4
作者：
Hoshino, T;Kawase, Y;Oizumi, K
通讯作者：
Oizumi, K