期刊
PHARMACOLOGY & THERAPEUTICS
卷 239, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2022.108189
关键词
Interleukin-12; Localized delivery; Viral vectors; Expression plasmids; And RNA-mediated delivery; Adoptive T cell therapy; Fusion proteins
资金
- Spanish Ministry of Economy and Competitiveness (MINECO) [SAF 2017-83267-C2-1R, PID2020-112892RB-100]
- Cancer Research Institute
- Asociacion Espanola Contra el Cancer (AECC) Foundation [GCB15152947MELE, TRS-2016-00000371, PI19/01128]
- Instituto de Salud Carlos III - European Union (ERDF)
- European Commission
- Gobierno de Navarra [0011-1411-2020000075]
- Fundacion BBVA
- European Union's Horizon 2020 research and innovation programmea under the Marie Sklodowska-Curie grant [765394]
Interleukin-12 is a potent agent for enhancing antitumor immune responses. Localized delivery methods such as electroporation and genetic engineering can significantly improve treatment outcomes, and combining IL-12 with checkpoint inhibitors shows promising results.
Interleukin-12 is considered a potent agent to enhance antitumor immune responses. It belongs to a family of heterodimeric cytokines with key roles in the up-regulation and down-regulation of cellular immunity. Since its discovery, recombinant IL-12 was found to exert potent antitumor effects in rodent tumor models and was rapidly tested in the clinic with an unfavorable benefit/toxicity profile. Localized delivery of IL-12 dramatically improves the therapeutic index and this approach is being applied in the clinic based on in-vivo electroporation of naked plasmid DNA encoding IL-12, mRNA formulations, viral vectors and tumor-targeted fusion proteins. Other biotechnology strategies such as IL-12-engineered local adoptive cell therapy and pro-cytokines can also be used to improve results and broaden the therapeutic window. Combination strategies of such localized IL-12-based approaches with checkpoint inhibitors are yielding promising results both preclinically and in the early-phase clinical trials.(c) 2022 Published by Elsevier Inc.
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