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Optimization of Microbubble‐Based DNA Vaccination with Low‐Frequency Ultrasound for Enhanced Cancer Immunotherapy
Author(s) -
Zhang Nisi,
Foiret Josquin,
Kheirolomoom Azadeh,
Liu Pei,
Feng Yi,
Tumbale Spencer,
Raie Marina,
Wu Bo,
Wang James,
Fite Brett Z.,
Dai Zhifei,
Ferrara Katherine W.
Publication year - 2021
Publication title -
advanced therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
0ISSN - 2366-3987
DOI - 10.1002/adtp.202100033
Subject(s) - immunotherapy , immune system , population , cancer research , transfection , cancer immunotherapy , cd8 , in vivo , gene delivery , medicine , immunology , biology , cell culture , environmental health , microbiology and biotechnology , genetics
Immunotherapy is an important cancer treatment strategy; nevertheless, the lack of robust immune cell infiltration in the tumor microenvironment remains a factor in limiting patient response rates. In vivo gene delivery protocols can amplify immune responses and sensitize tumors to immunotherapies, yet non‐viral transfection methods often sacrifice transduction efficiency for improved safety tolerance. To improve transduction efficiency, a strategy employing low ultrasound transmission frequency‐induced bubble oscillation is optimized to introduce plasmids into tumor cells. Differential centrifugation isolated size‐specific microbubbles (MBs). The diameter of the small MB population is 1.27 ± 0.89 µm and that of the larger population is 4.23 ± 2.27 µm. Upon in vitro insonation with the larger MB population, 29.7% of cancer cells are transfected with DNA plasmids, higher than that with smaller MBs (18.9%, P <0.05) or positive control treatments with a commercial transfection reagent (12%, P < 0.01). After 48 h, gene expression increases more than twofold in tumors treated with large, as compared with small, MBs. Furthermore, the immune response, including tumor infiltration of CD8 + T cells and F4/80 + macrophages, is enhanced. It is believed that this safe and efficacious method can improve preclinical procedures and outcomes for DNA vaccines in cancer immunotherapy in the future.