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Engineering Multi-Action Lipid Nanop...

Moon, Taylor,

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Engineering Multi-Action Lipid Nanoparticle Platforms for Cancer Immunotherapy /

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Engineering Multi-Action Lipid Nanoparticle Platforms for Cancer Immunotherapy // Taylor Moon.
作者:	Moon, Taylor,
面頁冊數:	1 electronic resource (162 pages)
附註:	Source: Dissertations Abstracts International, Volume: 86-08, Section: B.
Contained By:	Dissertations Abstracts International86-08B.
標題:	Nanotechnology. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31892197
ISBN:	9798302859952

Engineering Multi-Action Lipid Nanoparticle Platforms for Cancer Immunotherapy /
Moon, Taylor,

Engineering Multi-Action Lipid Nanoparticle Platforms for Cancer Immunotherapy /Taylor Moon. - 1 electronic resource (162 pages)

Source: Dissertations Abstracts International, Volume: 86-08, Section: B.

Cancer therapy has significantly advanced over the past few decades due to development of improved surgical technique, early detection, and novel therapy development. However, cancer remains one of the most lethal diseases due to metastasis, drug resistance, and recurrence. Immunotherapy holds the promise of utilizing the body's immune system to eliminate cancer cells. Immune checkpoint blockade therapy remains the most common utilization of immunotherapy in the clinical but yields varying degrees of success due to the massively immunosuppressed tumor microenvironment. Discovery of novel immune checkpoints and technology for targeting these checkpoints is critical for the advancement of cancer immunotherapy. The novel immune checkpoint protein VISTA (V-domain Immunoglobulin Suppressor of T cell Activation) impairs the toll-like receptor (TLR)-mediated activation of myeloid antigen presenting cells, promoting the expansion of myeloid derived suppressor cells, and suppressing tumor-reactive cytotoxic T cell function. Gene therapy targeting the VISTA checkpoint protein in conjunction with potent TLR agonists represents a safer yet potent alternative to antibody mediated cancer immunotherapy that has shown toxicity in the clinic. The overall objective of the work in this dissertation is to develop nanoparticle platforms for delivery of gene therapy mediate immune checkpoint blockade cancer immunotherapy regiments. First, a dual action lipid nanoparticle (Dual-LNP) that incorporates a VISTA-specific siRNA and a TLR9 agonist (unmethylated CPG) is developed. The Dual-LNP ensures co-delivery of both cargoes to tumor-infiltrating myeloid cells, leading to simultaneous silencing of VISTA and stimulation of TLR9. Next, the efficacy of the Dual-LNP was tested in multiple solid tumor models. The Dual-LNP treatment achieved a high cure rate in colon carcinoma MC38, melanoma B16F10, and YUMM1.7 models (83%, 60%, and 48%, respectively). Finally, investigation into the immune landscape was performed. Tumor rejection was associated with influx of immune cells to tumors and draining lymph nodes, dendritic cell activation, production of proinflammatory cytokines, and improved function of cytotoxic T cells. The improved response via T cell mediated action led to rejection of tumor recurrence as well. In conclusion, the following chapters will show that lipid nanoparticle mediated checkpoint blockade immunotherapies targeting myeloid immune cells are promising therapeutic platforms for treating immune-cold tumors.

English

ISBN: 9798302859952Subjects--Topical Terms:

526235
Nanotechnology.
Subjects--Index Terms:

Immunotherapy

Engineering Multi-Action Lipid Nanoparticle Platforms for Cancer Immunotherapy /
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