Melanoma treatment with intratumoral electroporation of tavokinogene telseplasmid (pIL-12, tavokinogene telseplasmid)

被引:48
作者
Canton, David A. [1 ]
Shirley, Shawna [1 ]
Wright, Jocelyn [1 ]
Connolly, Richard [1 ,2 ]
Burkart, Christoph [1 ]
Mukhopadhyay, Anandaroop [1 ]
Twitty, Chris [1 ]
Qattan, Kristen E. [1 ]
Campbell, Jean S. [2 ]
Le, Mai H. [2 ]
Pierce, Robert H. [2 ]
Gargosky, Sharron [1 ]
Daud, Adil [3 ]
Algazi, Alain [3 ]
机构
[1] OncoSec Med Inc, 5820 Nancy Ridge Dr, San Diego, CA 92121 USA
[2] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N, Seattle, WA 98109 USA
[3] UCSF Helen Diller Family Comprehens Canc Ctr, 1600 Divisadaro St, San Francisco, CA 94115 USA
关键词
cancer immunotherapy; cytokine; electroporation; gene therapy; IL-12; ImmunoPulse (R); IT-tavo-EP; melanoma; pIL-12; RECOMBINANT HUMAN INTERLEUKIN-12; SQUAMOUS-CELL CARCINOMA; COOPERATIVE-ONCOLOGY-GROUP; METASTATIC MELANOMA; ADJUVANT THERAPY; DNA VACCINE; OPEN-LABEL; PEMBROLIZUMAB; NIVOLUMAB; INTERFERON;
D O I
10.2217/imt-2017-0096
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
Tumors evade detection and/or clearance by the immune system via multiple mechanisms. IL-12 is a potent immunomodulatory cytokine that plays a central role in immune priming. However, systemic delivery of IL-12 can result in life-threatening toxicity and therefore has shown limited efficacy at doses that can be safely administered. We developed an electroporation technique to produce highly localized IL-12 expression within tumors leading to regression of both treated and untreated lesions in animal models and in patients with a favorable safety profile. Furthermore, intratumoral tavokinogene telseplasmid electroporation can drive cellular immune responses, converting 'cold' tumors into 'hot' tumors. Clinical trials are ongoing to determine whether intratumoral tavokinogene telseplasmid electroporation synergizes with checkpoint blockade therapy in immunologically cold tumors predicted not to respond to PD-1 antibody monotherapy.
引用
收藏
页码:1309 / 1321
页数:13
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