Powerful Anticolon Tumor Effect of Targeted Gene Immunotherapy
Using Folate-Modified Nanoparticle Delivery of CCL19 To Activate the
Immune System
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Version 2 2019-01-28, 14:03Version 2 2019-01-28, 14:03
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Posted on 2019-02-27 - 05:16
Targeted
gene delivery systems have recently shown potential clinical
benefits in cancer treatment. Recently, the immunologic therapies
application in cancer therapy also showed a continuously increase.
CCL19 has shown its great potential as a candidate immunomodulator
for colon cancer therapy by increasing the possibility of interaction
among dendritic cells, T and B cells in secondary lymphatic tissue,
thus regulating the primary (or secondary) adaptive immune responses.
In this work, a folic acid modified targeted gene-delivery system
consisting of DOTAP, MPEG-PLA, and Fa-PEG-PLA (F-DMA) was developed
successfully through a self-assembly approach. We proved that CCL19
expression was much higher in cancer cells after transfection with
F-DMA/CCL19 than after transfection with DMA/CCL19. The supernatant
from cancer cells transfected with both F-DMA/CCL19 and DMA/CCL19
stimulated the activation and cytotoxicity of T lymphocytes, the maturation
of DCs, and the polarization of macrophages in vitro. Moreover, the
administration of F-DMA/CCL19 complex to treat tumor-bearing mice
has shown significant cancer growth repression in both subcutaneous
and peritoneal models. The underling antitumor mechanism is established
through repressing neovascularization, promoting apoptosis, as well
as reducing proliferation by activating the immune system. The CCL19
plasmid and F-DMA complex may be used as a novel method for colorectal
cancer therapy in the clinic.
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Liu, Xiaoxiao; Wang, Bilan; Li, Yanyan; Hu, Yuzhu; Li, Xiaoling; Yu, Ting; et al. (2019). Powerful Anticolon Tumor Effect of Targeted Gene Immunotherapy
Using Folate-Modified Nanoparticle Delivery of CCL19 To Activate the
Immune System. ACS Publications. Collection. https://doi.org/10.1021/acscentsci.8b00688