Minicircle DNA-Mediated CAR T Cells Targeting CD44 Suppressed Hepatocellular Carcinoma Both in vitro and in vivo.

Abstract:

Purpose:Based on the continuous exploration of solid tumor immunotherapy, we focused on hepatocellular carcinoma with a high level of morbidity and mortality. We confirm the stability of mcDNA-based CAR T cell generating platform, and investigate the antitumor activity of CD44-CAR T cells against hepatocellular carcinoma both in vitro and in vivo. Materials and Methods:We fused anti-CD44 scFv structure with transmembrane domain and intracellular domain. Using a non-viral mcDNA vector to load CD44-CAR gene, then transfected the mcDNA-CD44-CAR into human T cells by electroporation. We exhibited the transfection efficacy of CAR T cells and the CD44 expression of tumor cell lines by flow cytometry. The antitumor efficacy of CD44-CAR T cells in vitro and in vivo was detected through CCK-8 and ELISA assays, and xenograft mouse models, respectively. Results:We obtained mcDNA-CD44-CAR with a high level of density after repeated extraction and purification. The expression efficacy of CD44-CAR in T cells was more than 50% after seven days electroporation and the phenotype of CD44-CAR T cells was no difference compared with normal T cells. For CD44-positive hepatocellular carcinoma xenograft mice, CD44-CAR T cells had stronger tumor growth suppression compared to normal T and mock T cells. The same results occurred on the in vitro experiments including cytokine secretion and cytotoxicity assays. H&E staining graphs revealed that CD44-CAR T cells did not induce side effects in xenograft mice. Conclusion:The strategy for generating CAR T cells targeting cancer stem cell antigens was efficient and concise. The mcDNA had superior transgene ability without virus-related adverse effects. CD44-CAR T cells had strong suppression capacity against hepatocellular carcinoma.

journal_name

Onco Targets Ther

journal_title

OncoTargets and therapy

authors

Wang H,Ye X,Ju Y,Cai Z,Wang X,Du P,Zhang M,Li Y,Cai J

doi

10.2147/OTT.S247836

subject

Has Abstract

pub_date

2020-05-04 00:00:00

pages

3703-3716

issn

1178-6930

pii

247836

journal_volume

13

pub_type

杂志文章
  • Single sternal metastasis due to malignant melanoma with unexpected long-term survival: a case report.

    abstract::Metastases from melanoma have a very poor prognosis for the patient. Single metastatic lesions in the sternum due to melanoma are extremely rare. A rare case of a presternal mass in a 56-year-old patient who had undergone excision for malignant melanoma is presented. Review of the patient's history and surgical resect...

    journal_title:OncoTargets and therapy

    pub_type:

    doi:10.2147/OTT.S95723

    authors: Gogakos AS,Paliouras D,Asteriou C,Rallis T,Lazopoulos A,Chatzinikolaou F,Zissimopoulos A,Tsavlis D,Tsirgogianni K,Zarogoulidis K,Porpodis K,Tsakiridis K,Pitsiou G,Kioumis I,Karapantzos I,Karapantzou C,Sachpekidis N,Zaro

    更新日期:2016-01-18 00:00:00

  • Restoration of miR-20a expression suppresses cell proliferation, migration, and invasion in HepG2 cells.

    abstract:OBJECTIVE:To study microRNA (miR)-20a expression in hepatocellular carcinoma (HCC) and its effects on the proliferation, migration, and invasion of HepG2. METHODS:The real-time polymerase chain reaction was used to detect the expression of miR-20a in HCC tissue and normal tissue, as well as in HCC cell lines and norma...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章

    doi:10.2147/OTT.S96861

    authors: Chen GS,Zhou N,Li JQ,Li T,Zhang ZQ,Si ZZ

    更新日期:2016-05-27 00:00:00

  • Bioinformatics analyses of differentially expressed genes associated with bisphosphonate-related osteonecrosis of the jaw in patients with multiple myeloma.

    abstract:PURPOSE:This study aimed to explore the molecular mechanisms associated with bisphosphonate (BP)-related osteonecrosis of the jaw (ONJ) in patients with multiple myeloma (MM). METHODS:The gene expression profile GSE7116 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) fro...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章

    doi:10.2147/OTT.S88463

    authors: Sun J,Wen X,Jin F,Li Y,Hu J,Sun Y

    更新日期:2015-09-22 00:00:00

  • The Expressions of Keratins and P63 in Primary Squamous Cell Carcinoma of the Thyroid Gland: An Application of Raman Spectroscopy.

    abstract:Purpose:Primary squamous cell carcinoma is a rare malignancy in the thyroid gland (SCCTh). The overall prognosis of this carcinoma is poor. This study aimed to explore the application of Raman spectroscopy in investigating the expression of CK5/6 and P63 in SCCTh. Patients and Methods:Tissues of the SCCTh and adjacent...

    journal_title:OncoTargets and therapy

    pub_type:

    doi:10.2147/OTT.S229436

    authors: Wang SS,Ye DX,Wang B,Xie C

    更新日期:2020-01-20 00:00:00

  • O-GlcNAcylation enhances the invasion of thyroid anaplastic cancer cells partially by PI3K/Akt1 pathway.

    abstract:BACKGROUND:The PI3K family participates in multiple signaling pathways to regulate cellular functions. PI3K/Akt signaling pathway plays an important role in tumorigenesis and development. O-GlcNAcylation, a posttranslational modification, is thought to modulate a wide range of biological processes, such as transcriptio...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章

    doi:10.2147/OTT.S82845

    authors: Zhang P,Wang C,Ma T,You S

    更新日期:2015-11-09 00:00:00

  • Alcoholic liver disease and risk of cholangiocarcinoma: a systematic review and meta-analysis.

    abstract:Background:With the purpose of elevating the risk of cholangiocarcinoma (CCA), alcoholic liver disease (ALD) was shown. Nonetheless, the findings were controversial. Herein, a meta-analysis and a systematic review were conducted to study the relation as mentioned above. Methods:This study searched PubMed, EMBASE, and ...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章

    doi:10.2147/OTT.S184444

    authors: Xiong J,Yin Z,Xu W,Shen Z,Li Y,Lu X

    更新日期:2018-11-20 00:00:00

  • CircRNA-PTN Sponges miR-326 to Promote Proliferation in Hepatocellular Carcinoma.

    abstract:Background:Mounting evidences reveal that circular RNAs (circRNAs) are critical to regulate biological behavior and process of tumor. Our objective is to explore the role of circRNA-PTN (circPTN) and explain the exact mechanism in hepatocellular carcinoma (HCC). Methods:Real-time polymerase chain reaction assay was us...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章

    doi:10.2147/OTT.S251300

    authors: Jia B,Yin X,Wang Y,Qian J,He Y,Yang C,Yu G,Guo B,Meng X

    更新日期:2020-05-29 00:00:00

  • The role and significance of VEGFR2+ regulatory T cells in tumor immunity.

    abstract::Tumor development is closely related to angiogenesis, and VEGFR2 plays an important role in tumor angiogenesis. It is broadly expressed in the blood vessels, especially in the microvessels of tumor tissues. Furthermore, VEGFR2 is detected on the surface of the cell membrane in various immune cells, such as dendritic c...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章,评审

    doi:10.2147/OTT.S142085

    authors: Zhu P,Hu C,Hui K,Jiang X

    更新日期:2017-09-01 00:00:00

  • Coincident primary breast lymphoma and gastrointestinal stromal tumor: case series and molecular mechanisms.

    abstract::Gastrointestinal stromal tumor (GIST) is an uncommon mesenchymal tumor, and has been shown to be associated with synchronous or metachronous second malignancies. Rare cases of coincident GIST and non-Hodgkin lymphomas (NHL) have been reported previously. Here, we report two cases of GIST and coincident primary breast ...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章

    doi:10.2147/OTT.S159843

    authors: Ludmir EB,Gutschenritter T,Pinnix CC,Gunther JR,Nastoupil LJ,Khoury JD,Medeiros LJ,Dabaja BS,Milgrom SA

    更新日期:2018-12-10 00:00:00

  • Irreversible electroporation combined with chemotherapy for unresectable pancreatic carcinoma: a prospective cohort study.

    abstract:Objective:We aimed to determine the safety and efficacy of irreversible electroporation (IRE) combined with chemotherapy for unresectable pancreatic carcinoma (stage III/IV). Methods:We prospectively enrolled 54 patients (30 men; median age 61.0 years; range 41-73 years) undergoing IRE with or without chemotherapy for...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章

    doi:10.2147/OTT.S186721

    authors: Liu S,Qin Z,Xu J,Zeng J,Chen J,Niu L,Xu M

    更新日期:2019-02-18 00:00:00

  • Noninvasive monitoring of the genetic evolution of EGFR-mutant non-small-cell lung cancer by analyzing circulating tumor DNA during combination chemotherapy with gefitinib and pemetrexed or S-1.

    abstract:BACKGROUND:Repetitive genotyping is useful to assess the genetic evolution of non-small-cell lung cancer (NSCLC) during treatment, but the need for sampling by biopsy is a major obstacle. Digital polymerase chain reaction (PCR) is a promising procedure for the detection of mutant alleles in plasma of cancer patients. ...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章

    doi:10.2147/OTT.S105976

    authors: Nakahara Y,Takagi Y,Hosomi Y,Kagei A,Yamamoto T,Sawada T,Yomota M,Okuma Y,Mikura S,Okamura T

    更新日期:2016-08-24 00:00:00

  • A DNA vaccine encoding mutated HPV58 mE6E7-Fc-GPI fusion antigen and GM-CSF and B7.1.

    abstract:BACKGROUND:Persistent infection with high-risk human papillomavirus (HPV) is a predominant cause of cervical cancer, and HPV58 is the third most common virus detected in the patients with cervical cancer in Asia. E6 and E7 are the viral oncogenes which are constitutively expressed in HPV-associated tumor cells and can ...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章

    doi:10.2147/OTT.S84888

    authors: Wang H,Yu J,Li L

    更新日期:2015-10-23 00:00:00

  • Prior EGFR tyrosine-kinase inhibitor therapy did not influence the efficacy of subsequent pemetrexed plus platinum in advanced chemonaïve patients with EGFR-mutant lung adenocarcinoma.

    abstract:BACKGROUND:Tumor cells before and after epidermal growth-factor receptor (EGFR) tyrosine-kinase inhibitor (TKI) therapy might display different characteristics. The aim of this study was to evaluate the influence of prior EGFR TKI therapy on the efficacy of subsequent pemetrexed plus platinum (PP) in advanced chemonaïv...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章

    doi:10.2147/OTT.S62639

    authors: Tseng JS,Yang TY,Chen KC,Hsu KH,Yu CJ,Liao WY,Tsai CR,Tsai MH,Yu SL,Su KY,Chen JJ,Chen HY,Chang GC

    更新日期:2014-05-23 00:00:00

  • Different setup errors assessed by weekly cone-beam computed tomography on different registration in nasopharyngeal carcinoma treated with intensity-modulated radiation therapy.

    abstract::The study aimed to investigate the difference of setup errors on different registration in the treatment of nasopharyngeal carcinoma based on weekly cone-beam computed tomography (CBCT). Thirty nasopharyngeal cancer patients scheduled to undergo intensity-modulated radiotherapy (IMRT) were prospectively enrolled in th...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章

    doi:10.2147/OTT.S87159

    authors: Su J,Chen W,Yang H,Hong J,Zhang Z,Yang G,Li L,Wei R

    更新日期:2015-09-14 00:00:00

  • The impact of tumor size change after target therapy on survival: analysis of patients enrolled onto three clinical trials of advanced NSCLC from one institution.

    abstract:PURPOSE:To explore whether changes in tumor size impact survival in advanced non-small-cell lung cancer (NSCLC) after target therapy, especially in patients with evaluation of stable disease (SD), and to review the applicability of the Response Evaluation Criteria in Solid Tumors (RECIST) criteria in target therapy. P...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章

    doi:10.2147/OTT.S38441

    authors: Zhang J,Huang Y,Li X,Guo Y,Zhao Y,Xue C,Hu Z,Zhang L,Zhao H

    更新日期:2012-01-01 00:00:00

  • Genetic ablation of TAZ induces HepG2 liver cancer cell apoptosis through activating the CaMKII/MIEF1 signaling pathway.

    abstract:Background and objective:Transcriptional coactivator with PDZ-binding motif (TAZ) has been found to be associated with tumor progression. Mitochondrial homeostasis regulates cancer cell viability and metastasis. However, the roles of TAZ and mitochondrial homeostasis in liver cancer viability have not been explored. Th...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章

    doi:10.2147/OTT.S196142

    authors: Hou Y,Lan C,Kong Y,Zhu C,Peng W,Huang Z,Zhang C

    更新日期:2019-03-01 00:00:00

  • Use of Programmed Death Receptor-1 and/or Programmed Death Ligand 1 Inhibitors for the Treatment of Brain Metastasis of Lung Cancer.

    abstract::The central nervous system (CNS) is regarded as an immune privileged environment; however, changes in the neuroimmunology paradigm have led to an increased interest in systematic immunotherapy in lung cancer therapy. The presence of the lymphatic system in the CNS as well as the physiological and biochemical changes i...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章,评审

    doi:10.2147/OTT.S235714

    authors: Wang S,Hu C,Xie F,Liu Y

    更新日期:2020-01-23 00:00:00

  • Identifying miRNA and gene modules of colon cancer associated with pathological stage by weighted gene co-expression network analysis.

    abstract:Introduction:Colorectal cancer (CRC) is the fourth most common cause of cancer-related mortality worldwide. The tumor, node, metastasis (TNM) stage remains the standard for CRC prognostication. Identification of meaningful microRNA (miRNA) and gene modules or representative biomarkers related to the pathological stage ...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章

    doi:10.2147/OTT.S163891

    authors: Zhou XG,Huang XL,Liang SY,Tang SM,Wu SK,Huang TT,Mo ZN,Wang QY

    更新日期:2018-05-15 00:00:00

  • Safety and Efficacy of Camrelizumab Combined with Apatinib for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Multicenter Retrospective Study.

    abstract:Introduction:Previous trials demonstrated that anti-angiogenesis or anti-programmed death protein 1 (PD-1) monotherapy showed unsatisfied effect in advanced hepatocellular carcinoma (HCC). No study existed that focus on the effects of camrelizumab and apatinib ("C+A") combination therapy for HCC patients with the locat...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章

    doi:10.2147/OTT.S286169

    authors: Yuan G,Cheng X,Li Q,Zang M,Huang W,Fan W,Wu T,Ruan J,Dai W,Yu W,Chen M,Guo Y,Hu X,Chen J

    更新日期:2020-12-09 00:00:00

  • The prognostic role of serum C-X-C chemokine receptor type 4 in patients with metastatic or recurrent colorectal cancer.

    abstract:BACKGROUND:C-X-C chemokine receptor type 4 (CXCR4) is involved in tumor progression including angiogenesis, metastasis, and survival. However, whether serum CXCR4 levels in metastatic or recurrent colorectal cancer have a prognostic role, have not been evaluated. METHODS:We analyzed serum samples from 55 patients with...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章

    doi:10.2147/OTT.S104511

    authors: Choi YJ,Chang WJ,Shin SW,Park KH,Kim ST,Kim YH

    更新日期:2016-06-01 00:00:00

  • FAM110B Inhibits Non-Small Cell Lung Cancer Cell Proliferation and Invasion Through Inactivating Wnt/β-Catenin Signaling.

    abstract:Purpose:FAM110B is a member of the FAM110 family (family with sequence similarity 110), which is a component of the centrosome associated proteins. Previous studies have shown that FAM110B may be involved in the process of cell cycle and may play a role in carcinogenesis and tumor progression. Using an online database,...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章

    doi:10.2147/OTT.S247491

    authors: Xie M,Cai L,Li J,Zhao J,Guo Y,Hou Z,Zhang X,Tian H,Li A,Miao Y

    更新日期:2020-05-19 00:00:00

  • Stereotactic body radiotherapy as the initial treatment for hepatocellular carcinoma with extensive inferior vena cava and atrium tumor thrombus.

    abstract::Hepatocellular carcinoma (HCC) with inferior vena cava (IVC) tumor thrombus rarely occurs, its prognosis is extremely poor. A 49-year-old locally advanced HCC male with tumor thrombus extension into the IVC and the right atrium was successfully treated with stereotactic body radiotherapy (SBRT). A radiation dose of 40...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章

    doi:10.2147/OTT.S208560

    authors: Shui Y,Zhu X,Wu J,Liang T,Wei Q

    更新日期:2019-07-04 00:00:00

  • Anterior gradient protein 3 is associated with less aggressive tumors and better outcome of breast cancer patients.

    abstract::Anterior gradient protein (AGR) 3 is a highly related homologue of pro-oncogenic AGR2 and belongs to the family of protein disulfide isomerases. Although AGR3 was found in breast, ovary, prostate, and liver cancer, it remains of yet poorly defined function in tumorigenesis. This study aimed to determine AGR3 expressio...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章

    doi:10.2147/OTT.S82235

    authors: Obacz J,Brychtova V,Podhorec J,Fabian P,Dobes P,Vojtesek B,Hrstka R

    更新日期:2015-06-24 00:00:00

  • Continuation of bevacizumab and addition of hormone therapy following weekly paclitaxel therapy in HER2-negative metastatic breast cancer.

    abstract:BACKGROUND:Bevacizumab plus taxane chemotherapy improves progression-free survival (PFS) versus taxane monotherapy in the first-line treatment of HER2-negative metastatic breast cancer (MBC) and appears promising in the second-line setting. This retrospective analysis evaluated the efficacy and safety of this combinati...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章

    doi:10.2147/OTT.S70654

    authors: Redondo A,Martínez V,Zamora P,Castelo B,Pinto A,Cruz P,Higuera O,Mendiola M,Hardisson D,Espinosa E

    更新日期:2014-11-27 00:00:00

  • Identification of COX5B as a novel biomarker in high-grade glioma patients.

    abstract:Background:Malignant glioma is the second leading cause of cancer-related death worldwide, and is known to exhibit a high degree of heterogeneity in its deregulation of different oncogenic pathways. The molecular subclasses of human glioma are not well known. Thus, it is crucial to identify vital oncogenic pathways in ...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章

    doi:10.2147/OTT.S139243

    authors: Hu T,Xi J

    更新日期:2017-11-15 00:00:00

  • p53 inhibits the expression of p125 and the methylation of POLD1 gene promoter by downregulating the Sp1-induced DNMT1 activities in breast cancer.

    abstract::p125 is one of four subunits of human DNA polymerases - DNA Pol δ as well as one of p53 target protein encoded by POLD1. However, the function and significance of p125 and the role that p53 plays in regulating p125 expression are not fully understood in breast cancer. Tissue sections of human breast cancer obtained fr...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章

    doi:10.2147/OTT.S98713

    authors: Zhang L,Yang W,Zhu X,Wei C

    更新日期:2016-03-10 00:00:00

  • Ocular basal cell carcinoma: a brief literature review of clinical diagnosis and treatment.

    abstract::Basal cell carcinoma (BCC) is a common malignant tumor throughout the world. One of the known risk factors of BCC is intense exposure to ultraviolet radiation. More than 50% of BCCs of the eyelid initially occur on the lower lid. The gold standard of diagnosis of BCC is histopathology. Treatment options for BCC consis...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章,评审

    doi:10.2147/OTT.S130371

    authors: Shi Y,Jia R,Fan X

    更新日期:2017-05-08 00:00:00

  • Stereotactic body radiotherapy or stereotactic ablative radiotherapy versus surgery for patients with T1-3N0M0 non-small cell lung cancer: a systematic review and meta-analysis.

    abstract:BACKGROUND:Stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy (SABR) has been reported to be a comparable alternative therapy to surgery for patients with T1-3N0M0 non-small cell lung cancer (NSCLC). However, it has not been clarified whether SBRT/SABR is as effective as surgery. We conducted t...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章

    doi:10.2147/OTT.S138701

    authors: Li M,Yang X,Chen Y,Yang X,Dai X,Sun F,Zhang L,Zhan C,Feng M,Wang Q

    更新日期:2017-06-07 00:00:00

  • Expression of novel tumor markers of pancreatic adenocarcinomas in intrahepatic cholangiocarcinomas.

    abstract::Intrahepatic cholangiocarcinomas (IHCCs) are morphologically and biologically similar to pancreatic ductal adenocarcinomas (PDACs), so newly identified PDAC-associated genes or proteins could provide clues for screening novel biomarkers for IHCC. In this study, the expression of three novel PDAC tumor markers (T-box t...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章

    doi:10.2147/OTT.S39646

    authors: Zong M,Jia L,Li L

    更新日期:2013-01-01 00:00:00

  • MiR-4766-5p Inhibits The Development And Progression Of Gastric Cancer By Targeting NKAP.

    abstract:Purpose:It is widely known that some specific microRNAs can regulate the expressions of genes in gastric cancer cells at the post-transcriptional level. Previous studies have identified that miRNA-4766-5p was involved in tumor cell proliferation and can be an independent prognostic indicator for malignant pleural mesot...

    journal_title:OncoTargets and therapy

    pub_type: 杂志文章

    doi:10.2147/OTT.S220234

    authors: Wei Y,Wang Y,Zang A,Wang Z,Fang G,Hong D

    更新日期:2019-10-16 00:00:00