Safety and efficacy of p62 DNA vaccine ELENAGEN in a first-in-human trial in patients with advanced solid tumors.
Safety and efficacy of p62 DNA vaccine ELENAGEN in a first-in-human trial in patients with advanced solid tumors.
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DOI：
10.18632/oncotarget.16574
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发表时间：
2017-08-08
期刊：
影响因子：
--
通讯作者：
Shneider AM
中科院分区：
文献类型：
--
作者：
Ponomarenko DM;Klimova ID;Chapygina YA;Dvornichenko VV;Zhukova NV;Orlova RV;Manikhas GM;Zyryanov AV;Burkhanova LA;Badrtdinova II;Oshchepkov BN;Filippova EV;Orlov SV;Kolesnikov SI;Sufianov AA;Baum SR;Zaitzeva OY;Komissarov AB;Grudinin MP;Kiselev OI;Tsyb AF;Venanzi F;Shcherbinina V;Chursov A;Gabai VL;Shneider AM
Elenagen 是编码 p62/SQSTM1 的质粒，是第一种具有两种相互补充的作用机制的 DNA 疫苗：它引发针对 p62 的免疫反应并减轻全身慢性炎症。此前，Elenagen 在啮齿动物肿瘤模型和犬自发性肿瘤中证明了抗肿瘤功效和安全性。这项多中心 I/IIa 试验评估了 Elenagen 在晚期实体瘤患者中的安全性和临床活性。 15 名患者接受递增剂量的 Elenagen 治疗（每剂 1-5 mg，每周 5 次），另外 12 名患者接受 1 mg 剂量。 10 名在 Elenagen 治疗后病情进展的乳腺癌和卵巢癌患者随后接受了常规化疗。不良事件（AE）为1级；没有观察到严重的 AE。累计 12 名患有乳腺癌、卵巢癌、肺癌、肾癌和黑色素瘤的患者疾病稳定至少 8 周，其中 4 名患者（15%）肿瘤控制时间超过 24 周，最长 32 周。乳腺癌和卵巢癌患者在 Elenagen 治疗后接受化疗后，肿瘤获得了额外的稳定 12-28 周。因此，Elenagen 在晚期实体瘤中表现出良好的安全性和抗肿瘤活性。尤其令人鼓舞的是它能够恢复肿瘤对化疗的敏感性。
Elenagen is a plasmid encoding p62/SQSTM1, the first DNA vaccine possessing two mutually complementing mechanisms of action: it elicits immune response against p62 and mitigates systemic chronic inflammation. Previously, Elenagen demonstrated anti-tumor efficacy and safety in rodent tumor models and spontaneous tumors in dogs. This multicenter I/IIa trial evaluated safety and clinical activity of Elenagen in patients with advanced solid tumors. Fifteen patients were treated with escalating doses of Elenagen (1- 5 mg per doses, 5 times weekly) and additional 12 patients received 1 mg dose. Ten patients with breast and ovary cancers that progressed after Elenagen were then treated with conventional chemotherapy. Adverse events (AE) were of Grade 1; no severe AE were observed. Cumulatively twelve patients (44%) with breast, ovary, lung, renal cancer and melanoma achieved stable disease for at least 8 wks, with 4 of them (15%) had tumor control for more than 24 wks, with a maximum of 32 wks. The patients with breast and ovary cancers achieved additional tumor stabilization for 12-28 wks when treated with chemotherapy following Elenagen treatment. Therefore, Elenagen demonstrated good safety profile and antitumor activity in advanced solid tumors. Especially encouraging is its ability to restore tumor sensitivity to chemotherapy.
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影响因子：
16
作者：
Kirkin, Vladimir;Lamark, Trond;Johansen, Terje
通讯作者：
Johansen, Terje
影响因子：
50.3
作者：
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Moscat, Jorge
影响因子：
5
作者：
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通讯作者：
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影响因子：
5.8
作者：
Chudley, Lindsey;McCann, Katy;Mander, Ann;Tjelle, Torunn;Campos-Perez, Juan;Godeseth, Rosemary;Creak, Antonia;Dobbyn, James;Johnson, Bernadette;Bass, Paul;Heath, Catherine;Kerr, Paul;Mathiesen, Iacob;Dearnaley, David;Stevenson, Freda;Ottensmeier, Christian
通讯作者：
Ottensmeier, Christian
DOI：
10.1126/science.aai9137
发表时间：
2016-10-14
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Dowd KA;Ko SY;Morabito KM;Yang ES;Pelc RS;DeMaso CR;Castilho LR;Abbink P;Boyd M;Nityanandam R;Gordon DN;Gallagher JR;Chen X;Todd JP;Tsybovsky Y;Harris A;Huang YS;Higgs S;Vanlandingham DL;Andersen H;Lewis MG;De La Barrera R;Eckels KH;Jarman RG;Nason MC;Barouch DH;Roederer M;Kong WP;Mascola JR;Pierson TC;Graham BS
通讯作者：
Graham BS