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Selective reversal of drug resistance in drug-resistant lung adenocarcinoma cells by tumor-specific expression of MDR1 ribozyme gene mediated by retrovirus

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Science China(Life Sciences) 1997年第2期40卷 122-127页

作者：高振强高志萍刘喜富张涛 Department of Pathology Beijing Medical University Beijing 100083 China

According to the fact that CEA gene expressed only in lung adenocarcinoma and not in normal lung cells, a retroviral vector (pCEAMR) was constructed which carried the CEA promoter coupled to MDR1 ribozyme gene. pCEAMR was introduced into drug-resistant lung adenocarcinoma cells GAOK with CEA expression and HeLaK without CEA expression; the expression of pCEAMR and drug resistance in the infected cells were analyzed in vitro and in vivo ; pCEAMR expressed only in CEA-producing GAOK cells and not in non-CEA-producing HeLa cells. The drug resistance to doxorubicin (DOX) decreased 91.5% in the infected GAOK cells and did not change in the infected HeLa cells. In nude mice, DOX could obviously inhibit the growth of the infected GAOK tumors, and had no effect on the growth of the infected HeLa cells. These results indicated that MDR1 ribozyme gene regulated by CEA promoter expressed only in human adenocarcinoma cells and reversed their drug resistance selectively. This gene-drug therapy might serve as an effective treatment method for patients with CEA-producing lung cancers which was usually refractory to conventional chemotherapy.

关键词： tumor-specific expression vector MDR1 rihozyme drug resistance human lung adenocarci- noma gene therapy.

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Selective gene therapy for human lung adenocarcinoma by tumor-specific expression of herpes simplex virus thymidine kinase gene

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Science China(Life Sciences) 1997年第4期40卷 430-436页

作者：高振强高志萍张涛刘喜富 Department of Pathology Beijing Medical University Beijing 100083 China

According to the fact that CEA gene expressed only in lung adenocarcinoma but not in normal lung cells, a retroviral expression vector (pCEATK) of the herpes simplex virus thymidine kinase (HSV-TK) gene regulated by CEA promoter was constructed and introduced into CEA-producing human lung adenocarcinoma cells GL and non-CEA-producing HeLa cells. The expression of pCEATK and Ganciclovir (GCV) sensitivity of the transfected cells were tested in vitro and in vivo . pCEATK expressed only in CEA-producing GL cells but not in non-CEA-producing HeLa cells. The sensitivity to GCV of pCEATK-transfected GL was 992 times higher compared with that of the parental cell line and there was obvious 'bystander effect' in vitro. HeLa cells transfected wtih pCEATK were still resistant to GCV. Injection of GCV resulted in significant regression of pCEATK-transfected GL tumors in nude mice. In addition, all mice with any fraction of GL cells expressing HSV-TK exhibited a significant reduction in tumor growth, including mice with only 10% of GL cells expressing HSV-TK. These results show the possibility of HSV-TK gene-drug therapy using the tumor-specific promoter of CEA gene against CEA-producing lung cancers which was usually refractory to conventional chemotherapy.

关键词： tumor-specific expression vector HSV-TK gene human lung adenocarcinoma gene therapy.

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Fluorescent traceable nanoparticles by co-self-assembly of carbon dot-drug conjugate and biodegradable hyperbranched polymer for diagnosis and therapy

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Particuology 2022年第3期20卷 79-87页

作者： Guoping Li Mingliang Pei Xinming Li Peng Liu State Key Laboratory of Applied Organic Chemistry College of Chemistry and Chemical EngineeringLanzhou UniversityLanzhou 730000China

Carbon dots(CDs)have attracted more interest in tumor theranostics,but they suffer from the rapid renal clearance due to small size and high *** solve such problems,hydrophobic pH-triggered carbon dot-drug conjugate(CDs-Hy-DOX)with high doxorubicin(DOX)content of 48.23%were designed by covalent conjugation of DOX onto the CDs via acid-labile linkage with hydrazine(Hy)as *** the fluorescent traceable hybrid prodrug nanoparticles were fabricated via co-self-assembly with the CDs-Hy-DOX as pH-sensitive prodrug and a pH/reduction dual-triggered degradable hyperbranched polymer PEG-PO-Cy as polyethylene glycol(PEG)-based surfactant,as well as gatekeeper for pH/reduction dual-triggered DOX *** hybrid prodrug nanoparticles with hydrodynamic diameter of 220 nm and DOX content of 22.99%were obtained with the optimized co-self-assembling *** could release 68.98%of DOX in the simulated tumor microenvironment within 3 days in a sustained release mode,with a premature drug leakage of 7.58%.After the acid-triggered DOX release from the CDs-Hy-DOX,which was accelerated by the pH/reduction dual-triggered degradation of the hyperbranched polymer,the strong fluorescence of CDs-Hy was recovered,demonstrating the promising potential in future tumor nanotheranostics.

关键词： tumor nanotheranostics Carbon dots Hyperbranched polymer tumor-specific Fluorescent imaging

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Colorectal cancer vaccines: tumor-associated antigens vs neoantigens

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World Journal of Gastroenterology 2018年第48期24卷 5418-5432页

作者： Sandra Wagner Christina S Mullins Michael Linnebacher Section of Molecular Oncology and Immunotherapy General SurgeryUniversity Medical Center

Therapeutic options for the treatment of colorectal cancer(CRC) are diverse but still not always satisfying. Recent success of immune checkpoint inhibition treatment for the subgroup of CRC patients suffering from hypermutated tumors suggests a permanent role of immune therapy in the clinical management of CRC. Substantial improvement in treatment outcome could be achieved by development of efficient patient-individual CRC vaccination strategies. This mini-review summarizes the current knowledge on the two general classes of targets: tumor-associated antigens(TAAs) and tumorspecific antigens. TAAs like carcinoembryonic antigen and melanoma associated antigen are present in and shared by a subgroup of patients and a variety of clinical studies examined the efficacy of different TAA-derived peptide vaccines. Combinations of several TAAs as the next step and the development of personalized TAA-based peptide vaccines are discussed. Improvements of peptidebased vaccines achievable by adjuvants and immunestimulatory chemotherapeutics are highlighted. Finally, we sum up clinical studies using tumor-specific antigens-in CRC almost exclusively neoantigens-which revealed promising results; particularly no severe adverse events were reported so far. Critical progress for clinical outcomes can be expected by individualizing neoantigen-based peptide vaccines and combining them with immunestimulatory chemotherapeutics and immune checkpoint inhibitors. In light of these data and latest developments, truly personalized neoantigen-based peptide vaccines can be expected to fulfill modern precision medicine's requirements and will manifest as treatment pillar for routine clinical management of CRC.

关键词： Cancer vaccines Colorectal neoplasm Immunotherapy Neoplasm antigen tumor-associated antigens tumor-specific antigens Neoantigen(s)

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