Cancer-Targeted BikDD Gene Therapy Elicits Protective Antitumor Immunity against Lung Cancer

Sher, Yuh Pyng; Liu, Shih‐Jen; Chang, Chun Mien; Lien, Shu Pei; Chen, Chien Hua; Han, Zhenbo; Li, Long-yuan; Chen, Jin‐Shing; Wu, Cheng Wen; Hung, Mien‐Chie

doi:10.1158/1535-7163.mct-10-0827

Cited by 13 publications

(7 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The activation of BIK has been confirmed to induce significant cancer cell death both in vivo and in vitro 30 . Moreover, gene therapy targeted on BikDD, a constitutively active mutant form of BIK, caused immune anticancer response in lung cancer 50 . Since our results revealed significant upregulation of BIK after SNHG17 knockdown, they indicate that the SNHG17/BIK axis has great potential in NSCLC gene-targeting therapy.…”

Section: Discussionsupporting

confidence: 53%

Gene Amplification-Driven Long Noncoding RNA SNHG17 Regulates Cell Proliferation and Migration in Human Non-Small-Cell Lung Cancer

Yan

Jiang

et al. 2019

Molecular Therapy - Nucleic Acids

View full text Add to dashboard Cite

Lung cancer is the most common cancer all around the world, with high morbidity and mortality. Long noncoding RNA (lncRNA) has been reported to have a critical role in non-small-cell lung cancer (NSCLC) proliferation and migration. In the present study, we analyzed The Cancer Genome Atlas (TCGA) data, and we found that lncRNA Small Nucleolar RNA Host Gene 17 (SNHG17) was upregulated in NSCLC driven by the amplification of copy number, indicating the special role of SNHG17 in NSCLC. The full exact length of SNHG17 was determined by rapid amplification of cDNA ends (RACE). We modulated SNHG17 expression by RNAi and a series of functional assays were performed. Flow cytometry was used to explore the involvement of SNHG17 in NSCLC cell apoptosis. Results showed that the knockdown of SNHG17 inhibited the proliferation and migration and promoted the apoptosis of NSCLC cells. We acquired the global gene expression profile regulated by SNHG17 in A549 through RNA sequencing (RNA-seq) assays. We found 637 genes were upregulated while 581 genes were downregulated. We selected three genes (FOXA1, XAF1, and BIK) that were closely related to proliferation and apoptosis, and we confirmed their altered expression in A549 and PC-9 cells treated with small interfering RNA si-SNHG17. Our findings indicated gene amplification-driven lncRNA SNHG17 promotes cell proliferation and migration in NSCLC, suggesting its potential value as a biomarker in NSCLC.

show abstract

Section: Discussionsupporting

confidence: 53%

Gene Amplification-Driven Long Noncoding RNA SNHG17 Regulates Cell Proliferation and Migration in Human Non-Small-Cell Lung Cancer

Yan

Jiang

et al. 2019

Molecular Therapy - Nucleic Acids

View full text Add to dashboard Cite

show abstract

“…TC-1 cancer cells (2 × 10 5 ) were inoculated into C57BL/6 mice by intravenous injection to establish an experimental animal model of metastatic lung cancer [41]. After 14 days, a single dose of PBS, rlipo-E7m, CpG or rlipo-E7m/CpG was subcutaneously injected into the mice to evaluate the therapeutic effects of these compounds.…”

Section: Methodsmentioning

confidence: 99%

Toll-like receptor 9 agonist enhances anti-tumor immunity and inhibits tumor-associated immunosuppressive cells numbers in a mouse cervical cancer model following recombinant lipoprotein therapy

et al. 2014

Self Cite

View full text Add to dashboard Cite

BackgroundAlthough cytotoxic T lymphocytes (CTLs) play a major role in eradicating cancer cells during immunotherapy, the cancer-associated immunosuppressive microenvironment often limits the success of such therapies. Therefore, the simultaneous induction of cancer-specific CTLs and reversal of the immunosuppressive tumor microenvironment may be more effectively achieved through a single therapeutic vaccine. A recombinant lipoprotein with intrinsic Toll-like receptor 2 (TLR2) agonist activity containing a mutant form of E7 (E7m) and a bacterial lipid moiety (rlipo-E7m) has been demonstrated to induce robust CTL responses against small tumors. This treatment in combination with other TLR agonists is able to eliminate large tumors.MethodsMouse bone marrow-derived dendritic cells (DCs) were employed to determine the synergistic production of pro-inflammatory cytokines upon combination of rlipo-E7m and other TLR agonists. Antigen-specific CTL responses were investigated using immunospots or in vivo cytolytic assays after immunization in mice. Mice bearing various tumor sizes were used to evaluate the anti-tumor effects of the formulation. Specific subpopulations of immunosuppressive cells in the tumor infiltrate were quantitatively determined by flow cytometry.ResultsWe demonstrate that a TLR9 agonist (unmethylated CpG oligodeoxynucleotide, CpG ODN) enhances CTL responses and eradicates large tumors when combined with rlipo-E7m. Moreover, combined treatment with rlipo-E7m and CpG ODN effectively increases tumor infiltration by CTLs and reduces the numbers of myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs) and regulatory T cells (Tregs) in the tumor microenvironment.ConclusionThese findings suggest that the dramatic anti-tumor effects of the recombinant lipoprotein together with CpG ODN may reflect the amplification of CTL responses and the repression of the immunosuppressive environment. This promising approach could be applied for the development of additional therapeutic cancer vaccines.

show abstract

“…For the mouse lung cancer models, 1 × 10 6 wild-type (TC1-WT) or ADAM9 knockout (TC1-ADAM9 KO) TC1 cells were injected subcutaneously into the flanks of C57BL/6 mice at 6 weeks of age. The size of subcutaneous tumors was calculated by the formula V (mm 3 ) = a × b 2 /2, where a is the largest dimension and b is the perpendicular diameter 49 . For the metastatic model, TC1-WT or TC1-ADAM9 KO cells (1 × 10 6 ) were intravenously injected via the tail vein of the mouse at 6 weeks of age.…”

Section: Methodsmentioning

confidence: 99%

ADAM9 promotes lung cancer progression through vascular remodeling by VEGFA, ANGPT2, and PLAT

Lin

Cho

Bai

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

Lung cancer has a very high prevalence of brain metastasis, which results in a poor clinical outcome. Up-regulation of a disintegrin and metalloproteinase 9 (ADAM9) in lung cancer cells is correlated with metastasis to the brain. However, the molecular mechanism underlying this correlation remains to be elucidated. Since angiogenesis is an essential step for brain metastasis, microarray experiments were used to explore ADAM9-regulated genes that function in vascular remodeling. The results showed that the expression levels of vascular endothelial growth factor A (VEGFA), angiopoietin-2 (ANGPT2), and tissue plasminogen activator (PLAT) were suppressed in ADAM9-silenced cells, which in turn leads to decreases in angiogenesis, vascular remodeling, and tumor growth in vivo. Furthermore, simultaneous high expression of ADAM9 and VEGFA or of ADAM9 and ANGPT2 was correlated with poor prognosis in a clinical dataset. These findings suggest that ADAM9 promotes tumorigenesis through vascular remodeling, particularly by increasing the function of VEGFA, ANGPT2, and PLAT.

show abstract

Cancer-Targeted BikDD Gene Therapy Elicits Protective Antitumor Immunity against Lung Cancer

Cited by 13 publications

References 28 publications

Gene Amplification-Driven Long Noncoding RNA SNHG17 Regulates Cell Proliferation and Migration in Human Non-Small-Cell Lung Cancer

Gene Amplification-Driven Long Noncoding RNA SNHG17 Regulates Cell Proliferation and Migration in Human Non-Small-Cell Lung Cancer

Toll-like receptor 9 agonist enhances anti-tumor immunity and inhibits tumor-associated immunosuppressive cells numbers in a mouse cervical cancer model following recombinant lipoprotein therapy

ADAM9 promotes lung cancer progression through vascular remodeling by VEGFA, ANGPT2, and PLAT

Contact Info

Product

Resources

About