Intratumoral Gene Transfer of mRNAs Encoding IL12 in Combination with Decoy-Resistant IL18 Improves Local and Systemic Antitumor Immunity

被引：11

作者：

Cirella, Assunta ^{[1
,2
]}

Bolanos, Elixabet ^{[1
,2
]}

Di Trani, Claudia Augusta ^{[1
,2
]}

de Andrea, Carlos E. ^{[2
,3
,4
,5
]}

Sanchez-Gregorio, Sandra ^{[1
,2
]}

Etxeberria, Inaki ^{[1
,2
]}

Gonzalez-Gomariz, Jose ^{[1
,2
]}

Olivera, Irene ^{[1
,2
]}

Brocco, Davide ^{[6
]}

Glez-Vaz, Javier ^{[1
,2
]}

Luri-Rey, Carlos ^{[1
,2
]}

Azpilikueta, Arantza ^{[1
,2
]}

Rodriguez, Inmaculada ^{[1
,2
]}

Fernandez-Sendin, Myriam ^{[1
,2
]}

Egea, Josune ^{[1
,2
]}

Eguren, Inaki ^{[1
,2
]}

Sanmamed, Miguel F. ^{[1
,2
,5
,7
]}

Palencia, Belen ^{[1
,2
]}

Teijeira, Alvaro ^{[1
,2
,5
]}

Berraondo, Pedro ^{[1
,2
,5
]}

Melero, Ignacio ^{[1
,2
,5
,7
,8
]}

机构：

[1] Cima Univ Navarra, Program Immunol & Immunotherapy, Pamplona, Spain

[2] Navarra Inst Hlth Res IDISNA, Pamplona, Spain

[3] Univ Navarra, Clin Univ Navarra, Dept Pathol, Pamplona, Spain

[4] Univ Navarra, Dept Anat Physiol & Pathol, Pamplona, Spain

[5] Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain

[6] Univ G dAnnunzio, Dept Pharm, Chieti, Italy

[7] Clin Univ Navarra, Dept Oncol, Madrid, Spain

[8] Clin Univ Navarra, Dept Immunol & Immunotherapy, Pamplona, Spain

来源：

CANCER IMMUNOLOGY RESEARCH | 2023年 / 11卷 / 02期

关键词：

IFN-GAMMA PRODUCTION; DENDRITIC CELLS; CANCER-IMMUNOTHERAPY; HUMAN INTERLEUKIN-12; IL-12; INJECTION; ACTIVATION; REGRESSION; EXPRESSION; DELIVERY;

D O I：

10.1158/2326-6066.CIR-22-0373

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

IL12-based local gene therapy of cancer constitutes an active area of clinical research using plasmids, mRNAs, and viral vectors. To improve antitumor effects, we have experimentally tested the combination of mRNA constructs encoding IL12 and IL18. More-over, we have used a form of IL18 [decoy-resistant IL18 (DR-18)] which has preserved bioactivity but does not bind to the IL18 binding protein decoy receptor. Both cytokines dramatically syner-gize to induce IFNy release from mouse splenocytes, and, if systemically cotransferred to the liver, they mediate lethal toxicity. However, if given intratumorally to B16OVA tumor-bearing mice,

引用

页码：184 / 198

页数：15

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