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Artificial Immunogenic Cell Death Lipid Nanoparticle Functions as a Therapeutic Vaccine for Cancer |
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| Authors: | So-Jung Kim Hae-Bin Park Eun-Koung An Hee-Yun Eom Wei Zhang Jihoe Kim Inho Choi Minseok Kwak Peter C W Lee Jun-O Jin |
| Affiliation: | 1. Department of Microbiology, University of Ulsan College of Medicine, ASAN Medical Center, Seoul, 05505 South Korea;2. Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508 China;3. Department of Medical Biotechnology, Yeungnam University, Gyeongsan, 38541 South Korea
Research Institute of Cell Culture, Yeungnam University, Gyeongsan, 38541 South Korea;4. Department of Chemistry, Pukyong National University, Busan, 48513 South Korea;5. Department of Biomedical Sciences, University of Ulsan College of Medicine, ASAN Medical Center, Seoul, 05505 South Korea Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, ASAN Medical Center, Seoul, 05505 South 6. Korea |
| Abstract: | Anticancer drug-mediated induction of immunogenic cell death (ICD) blocks metastasis or recurrence in cancer cells by promoting specific immune activity against cancer antigens. However, this strategy has failed to afford adequate treatment efficiency. Overcoming the failure of ICD-mediated cancer therapy, lipid nanoparticles (LNPs) containing cancer cell surface proteins are synthesized using sonication and extrusion without microfluidics. In addition, these LNPs are decorated with high-mobility group box 1 protein and calreticulin, indicators of ICD, and named artificial ICD LNPs (AiLNPs). Administration of AiLNPs effectively targets dendritic cells (DCs) and induces DC activation in mice. Moreover, treating CT-26 tumor-bearing mice with AiLNPs inhibits tumor growth by inducing CT-26 antigen-specific T-cell immunity. Furthermore, AiLNPs containing Lewis lung carcinoma (LLC1) membrane proteins can prevent metastatic LLC1 tumor growth in the lung via LLC1 antigen-specific T-cell activation. Finally, AiLNPs synthesized with human breast cancer membrane proteins activate DC-mediated antigen-specific T-cell immunity, effectively killing tumor cells. Therefore, AiLNPs are expected to be developed as a patient-specific cancer treatment to prevent cancer recurrence and metastasis. |
| Keywords: | anticancer antigen-specific immune responses cytotoxic T lymphocytes immunogenic cell deaths lipid nanoparticles |