Immunoliposome-based targeted delivery of the CRISPR/Cas9gRNA-IL30 complex inhibits prostate cancer and prolongs survival
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The development of selective and nontoxic immunotherapy targeting prostate cancer (PC) is challenging. Interleukin (IL)30 plays immunoinhibitory and oncogenic roles in PC, and its tumor-specific suppression may have significant clinical implications. CRISPR/Cas9-mediated IL30 gene deletion in PC xenografts using anti-PSCA antibody-driven lipid nanocomplexes (Cas9gRNA-hIL30-PSCA NxPs) revealed significant genome editing efficiency and circulation stability without off-target effects or organ toxicity. Biweekly intravenous administration of Cas9gRNA-hIL30-PSCA NxPs to PC-bearing mice inhibited tumor growth and metastasis and improved survival. Mechanistically, Cas9gRNA-hIL30-PSCA NxPs suppressed ANGPTL 1/2/4, IL1β, CCL2, CXCL1/6, SERPINE1-F1, EFNB2, PLG, PF4, VEGFA, VEGFD, ANG, TGFβ1, EGF and HGF expression in human PC cells while upregulated CDH1, DKK3 and PTEN expression, leading to low proliferation and extensive ischemic necrosis. In the syngeneic PC model, IL30-targeting immunoliposomes downregulated NFKB1 expression and prevented intratumoral influx of CD11b+Gr-1+MDCs, Foxp3+Tregs, and NKp46+RORγt+ILC3, and prolonged host survival by inhibiting tumor progression. This study serves as a proof of principle that immunoliposome-based targeted delivery of Cas9gRNA-IL30 represent a potentially safe and effective strategy for PC treatment.
Abstract
The development of selective and nontoxic immunotherapy targeting prostate cancer (PC) is challenging. Interleukin (IL)30 plays immunoinhibitory and oncogenic roles in PC, and its tumor-specific suppression may have significant clinical implications. CRISPR/Cas9-mediated IL30 gene deletion in PC xenografts using anti-PSCA antibody-driven lipid nanocomplexes (Cas9gRNA-hIL30-PSCA NxPs) revealed significant genome editing efficiency and circulation stability without off-target effects or organ toxicity. Biweekly intravenous administration of Cas9gRNA-hIL30-PSCA NxPs to PC-bearing mice inhibited tumor growth and metastasis and improved survival. Mechanistically, Cas9gRNA-hIL30-PSCA NxPs suppressed ANGPTL 1/2/4, IL1β, CCL2, CXCL1/6, SERPINE1-F1, EFNB2, PLG, PF4, VEGFA, VEGFD, ANG, TGFβ1, EGF and HGF expression in human PC cells while upregulated CDH1, DKK3 and PTEN expression, leading to low proliferation and extensive ischemic necrosis. In the syngeneic PC model, IL30-targeting immunoliposomes downregulated NFKB1 expression and prevented intratumoral influx of CD11b+Gr-1+MDCs, Foxp3+Tregs, and NKp46+RORγt+ILC3, and prolonged host survival by inhibiting tumor progression. This study serves as a proof of principle that immunoliposome-based targeted delivery of Cas9gRNA-IL30 represent a potentially safe and effective strategy for PC treatment.
참고문헌 (63)
- Siegel, R. L., "Cancer statistics", CA Cancer J. Clin, 72, pp.7~33 (2022)
- Cheng, Z., "Nanomaterials for cancer therapy : current progress and perspectives", J. Hematol. Oncol, 14, pp.85~ (2021)
- Liu, P., "A review of liposomes as a drug delivery system : current status of approved products, regulatory environments, and future per spectives", Molecules, 27, pp.1372~ (2022)
- Sonju, J. J., "Peptide-functionalized liposomes as therapeutic and diagnostic tools for cancer treatment", J. Control. Release, 329, pp.624~644 (2021)
- Markowski, A., "Novel liposomal formulation of baicalein for the treatment of pancreatic ductal adenocarcinoma : design, characterization, and evaluation", Pharmaceutics, 15, pp.179~ (2023)
- Pflanz, S., "IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4+ T cells", Immunity, 16, pp.779~790 (2002)
- Di Meo, S., "Interleukin-30 expression in prostate cancer and its draining lymph nodes correlates with advanced grade and stage", Clin. Cancer Res, 20, pp.585~594 (2014)
- Airoldi, I., "Interleukin-30 promotes breast cancer growth and progression", Cancer Res, 76, pp.6218~6229 (2016)
- Sorrentino, C., "Interleukin-30", IL27p28 shapes prostate cancer stem-like cell behavior and is critical for tumor onset and metastasization, 2018, pp.78, 2654~2668
- Müller, S. I., "A folding switch regulates interleukin 27 biogenesis and secretion of its α-subunit as a cytokine", Proc. Natl Acad. Sci. USA, 116, pp.1585~1590 (2019)
- Sorrentino, C., "Interleukin-30 feeds breast cancer stem cells via CXCL10 and IL23 autocrine loops and shapes immune contexture and host outcome", J. Immunother. Cancer, 9, pp.e002966~ (2021)
- Sorrentino, C., "CRISPR", Cas9-mediated deletion of Interleukin-30 suppresses IGF1 and CXCL5 and boosts SOCS3 reducing prostate cancer growth and mor tality, 2022, pp.15, 145~
- Knott, G. J., "CRISPR-Cas guides the future of genetic engineering", Science, 361, pp.866~869 (2018)
- Kaushik, I., "CRISPR-Cas9 : a multifaceted therapeutic strategy for cancer treatment", Semin. Cell. Dev. Biol, 96, pp.4~12 (2019)
- Stone, K. R., "Isolation of a human prostate carcinoma cell line(DU 145)", Int. J. Cancer, 21, pp.274~281 (1978)
- Tai, S., "PC3 is a cell line characteristic of prostatic small cell carcinoma", Prostate, 71, pp.1668~1679 (2011)
- Foster, B. A., "Char acterization of prostatic epithelial cell lines derived from transgenic adenocarci noma of the mouse prostate(TRAMP)model", Cancer Res, 57, pp.3325~3330 (1997)
- Brinkman, E. K., "Rapid quantitative evaluation of CRISPR gen ome editing by TIDE and TIDER", Methods Mol. Biol, 1961, pp.29~44 (2019)
- Conant, D., "Inference of CRISPR edits from Sanger trace data", CRISPR J, 5, pp.123~130 (2022)
- Gu, Z., "Prostate stem cell antigen(PSCA)expression increases with high Gleason score, advanced stage and bone metastasis in prostate cancer", Oncogene, 19, pp.1288~1296 (2000)
- Lam, J. S., "Prostate stem cell antigen is overexpressed in prostate cancer metastases", Clin. Cancer Res, 11, pp.2591~2596 (2005)
- Ghosh, S., "Nanomaterials Safety: Toxicity And Health Hazards", pp.207~214 (2019), De Gruyter
- Ritsma, L., "Intravital microscopy through an abdominal imaging window reveals a pre-micrometastasis stage during liver metastasis", Sci. Transl. Med, 4, pp.158ra145~ (2012)
- Nguyen, D. P., "Recent insights into NF-κB sig nalling pathways and the link between inflammation and prostate cancer", BJU Int, 114, pp.168~176 (2014)
- Schmitz, M., "Complete loss of PTEN expression as a possible early prognostic marker for prostate cancer metastasis", Int. J. Cancer, 120, pp.1284~1292 (2007)
- van Berlo, D., "10% Body weight(gain)change as criterion for the maximum tolerated dose : a critical analysis", Regul. Toxicol. Pharmacol, 134, pp.105235~ (2022)
- Sorrentino, C., "Hindering triple negative breast cancer progression by tar geting endogenous interleukin-30 requires IFNγ signaling", Clin. Transl. Med, 11, pp.e278~ (2021)
- Taniguchi, K., "NF-κB, inflammation, immunity and cancer : coming of age", Nat. Rev. Immunol, 18, pp.309~324 (2018)
- Waldman, A. D., "A guide to cancer immunotherapy : from T cell basic science to clinical practice", Nat. Rev. Immunol, 20, pp.651~668 (2020)
- Sorrentino, C., "Targeting Interleukin(IL)-30", IL-27p28 signaling in cancer stem like cells and host environment synergistically inhibits prostate cancer growth and improves survival, 2019, pp.7, 201~
- Doudna, J. A., "Genome editing. The new frontier of genome engineering with CRISPR-Cas9", Science, 346, pp.1258096~ (2014)
- Kanduri, V., "Current advances toward the encapsulation of Cas9", ACS Macro Lett, 10, pp.1576~1589 (2021)
- Immordino, M. L., "Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential", Int. J. Nanomed, 1, pp.297~315 (2006)
- Andresen, T. L., "Advanced strategies in liposomal cancer therapy: problems and prospects of active and tumor specific drug release", Prog. Lipid Res, 44, pp.68~97 (2005)
- Suk, J. S., "PEGylation as a strategy for improving nanoparticle-based drug and gene delivery", Adv. Drug Deliv. Rev, 99, pp.28~51 (2016)
- Du, Z., "The role of the helper lipid on the DNA transfection efficiency of lipopolyplex formulations", Sci. Rep, 4, pp.7107~ (2014)
- Marques, A. C., "Lipid nanoparticles functiona lized with antibodies for anticancer drug therapy", Pharmaceutics, 15, pp.216~ (2023)
- Ciummo, S. L., "Interleukin-30 subverts prostate cancer-endothelium crosstalk by fostering angiogenesis and activating immunoregulatory and oncogenic signaling pathways", J. Exp. Clin. Cancer Res, 42, pp.336~ (2023)
- Jacobo, S. M., "Insulin-like growth factor 1 (IGF-1) stabilizes nas cent blood vessels", J. Biol. Chem, 290, pp.6349~6360 (2015)
- Hall-Glenn, F., "CCN2", connective tissue growth factor is essential for pericyte adhesion and endothelial basement membrane formation during angiogenesis, 2012, pp.7, e30562~
- Keeley, E. C., "CXC chemokines in cancer angiogenesis and metastases", Adv. Cancer Res, 106, pp.91~111 (2010)
- Bagnato, A., "Emerging role of endothelin-1 in tumor angiogenesis", Trends Endocrinol. Metab, 14, pp.44~50 (2003)
- Nakagawa, T., "Inhibition of angiogenesis and tumor progression of MK-0429, an integrin αvβ3 antagonist, on oral squamous cell carcinoma", J. Cancer Res. Clin. Oncol, 148, pp.3281~3292 (2022)
- Sainson, R. C., "TNF primes endothelial cells for angiogenic sprouting by inducing a tip cell phenotype", Blood, 111, pp.4997~5007 (2008)
- Quintero-Fabián, S., "Role of matrix metalloproteinases in angiogenesis and cancer", Front. Oncol, 9, pp.1370~ (2019)
- Murakami, M., "Fibroblast growth factor regulation of neovascular ization", Curr. Opin. Hematol, 15, pp.215~220 (2008)
- Iñiguez, M. A., "Cycloox ygenase-2 : a therapeutic target in angiogenesis", Trends Mol. Med, 9, pp.73~78 (2003)
- Pećina-Slaus, N., "Tumor suppressor gene E-cadherin and its role in normal and malignant cells", Cancer Cell. Int, 3, pp.17~ (2003)
- Kardooni, H., "CRISPR-mediated reactivation of DKK3 expression attenuates TGF-β Signaling in prostate cancer", Cancers, 10, pp.165~ (2018)
- Lee, E. J., "Dickkopf-3 in human malignant tumours: a clinical viewpoint", Anticancer Res, 40, pp.5969~5979 (2020)
- Chen, C. Y., "PTEN : tumor suppressor and metabolic regulator", Front. Endocrinol, 9, pp.338~ (2018)
- Karpisheh, V., "The role of regulatory T cells in the pathogenesis and treat ment of prostate cancer", Life Sci, 284, pp.119132~ (2021)
- Irshad, S., "RORγt+ innate lymphoid cells promote lymph node metastasis of breast cancers", Cancer Res, 77, pp.1083~1096 (2017)
- Koh, J., "IL23-producing human lung cancer cells promote tumor growth via conversion of innate lymphoid cell 1(ILC1)into ILC3", Clin. Cancer Res, 25, pp.4026~4037 (2019)
- Bal, S. M., "Plasticity of innate lymphoid cell subsets", Nat. Rev. Immunol, 20, pp.552~565 (2020)
- Bergers, G., "Modes of resistance to anti-angiogenic therapy", Nat. Rev. Cancer, 8, pp.592~603 (2008)
- Haibe, Y., "Resistance mechanisms to anti-angiogenic therapies in cancer", Front. Oncol, 10, pp.221~ (2020)
- Lee, W. S., "Combination of anti-angiogenic therapy and immune checkpoint blockade normalizes vascular-immune crosstalk to potentiate cancer immunity", Exp. Mol. Med, 52, pp.1475~1485 (2020)
- Sharma, R., "Determinants of resistance to VEGF-TKI and immune checkpoint inhibitors in metastatic renal cell carcinoma", J. Exp. Clin. Cancer Res, 40, pp.186~ (2021)
- Beltrán-Gracia, E., "Nanomedicine review : clinical developments in liposomal applications", Cancer Nano, 10, pp.11~ (2019)
- Rommasi, F., "Liposomal nanomedicine : applications for drug delivery in cancer therapy", Nanoscale Res. Lett, 16, pp.95~ (2021)
- Rehman, L. U., "Immunotherapy for prostate cancer : a current systematic review and patient centric perspectives", J. Clin. Med, 12, pp.1446~ (2023)
- Sorrentino, C., "Molecular targeted therapies in metastatic prostate cancer : recent advances and future challenges", Cancers, 15, pp.2885~ (2023)
