scholarly journals Assessing and Overcoming Resistance Phenomena against a Genetically Modified Vaccinia Virus in Selected Cancer Cell Lines

2020 ◽  
Vol 21 (20) ◽  
pp. 7618
Author(s):  
Susanne Berchtold ◽  
Julia Beil ◽  
Christian Raff ◽  
Irina Smirnow ◽  
Martina Schell ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Clinical Success ◽  
Genetically Modified ◽  
Cell Mass ◽  
Cytosine Deaminase ◽  
Resistance Pattern ◽  
Primary Resistance ◽  
Replication Studies ◽  
Vaccinia Viruses

Genetically modified vaccinia viruses (VACVs) have been shown to possess profound oncolytic capabilities. However, tumor cell resistance to VACVs may endanger broad clinical success. Using cell mass assays, viral replication studies, and fluorescence microscopy, we investigated primary resistance phenomena of cell lines of the NCI-60 tumor cell panel to GLV-1h94, a derivative of the Lister strain of VACV, which encodes the enzyme super cytosine deaminase (SCD) that converts the prodrug 5-fluorocytosine (5-FC) into the chemotherapeutic compound 5-fluorouracil (5-FU). After treatment with GLV-1h94 alone, only half of the cell lines were defined as highly susceptible to GLV-1h94-induced oncolysis. When adding 5-FC, 85% of the cell lines became highly susceptible to combinatorial treatment; none of the tested tumor cell lines exhibited a “high-grade resistance” pattern. Detailed investigation of the SCD prodrug system suggested that the cytotoxic effect of converted 5-FU is directed either against the cells or against the virus particles, depending on the balance between cell line-specific susceptibility to GLV-1h94-induced oncolysis and 5-FU sensitivity. The data provided by this work underline that cellular resistance against VACV-based virotherapy can be overcome by virus-encoded prodrug systems. Phase I/II clinical trials are recommended to further elucidate the enormous potential of this combination therapy.

scholarly journals An Fc-Engineered CD133 Antibody for Induction of NK Cell Reactivity Against Cancer Cells

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2739-2739
Author(s):  
Kathrin Rothfelder ◽  
Julia Leibold ◽  
Ludger Grosse-Hovest ◽  
Hans-Joerg Buehring ◽  
Gundram Jung ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cancer Cells ◽  
Solid Tumors ◽  
Cell Lines ◽  
Nk Cell ◽  
Conflicts Of Interest ◽  
Clinical Success ◽  
Cell Reactivity ◽  
Immunotherapy Of Cancer ◽  
Novel Strategy

Abstract CD133 is expressed in various types of solid tumors where it predicts an unfavourable clinical outcome (e.g. Linuma et al., J Clin Oncol. 2011). Moreover, CD133 has been shown to be preferentially expressed by cancer stem cells (CSC), as e.g. demonstrated by its usability to enrich CSCs containing populations within cancer cell preparations (e.g. Zeppernick et al., Nature 2008). As CSC display marked resistance to chemo- and radiation therapy, great efforts are presently made to develop immunotherapeutic approaches to specifically target CSC without harming healthy tissue. We here report on the preclinical characterization of a monoclonal antibody (mAb) directed towards CD133 for induction of NK cell reactivity against cancer cells. Two different anti-CD133 antibody clones (W6B3 and 293C3) were used to study expression levels of CD133 in different cell lines derived from solid tumors (A172 and U87MG, glioblastoma; CaCo-2, Colo-205, HCT-8, HT-29 and SW48, colorectal cancer; MDA-MB-231, MDA-MB-468 and BT474, breast cancer; WERI-Rb1, retinoblastoma). CD133 was recognized by W6B3 and 293C3 in 4 and 5 out of the 11 cell lines, respectively. The latter mAb was then chosen for the development of chimeric mAbs with either a wildtype human Fc part (293C3-WT) or a variant containing amino acid exchanges (S239D/I332E) to enhance its affinity to the activating Fc receptor CD16 (293C3-SDIE) and thereby its capacity to mediate antibody dependent cellular cytotoxicity (ADCC), an important antibody property that largely contributes to the clinical success of antitumor mAbs. After confirming the binding specificity of both 293C3-WT and 293C3-SDIE we employed cytotoxicity assays to comparatively analyze their ability to induce NK cell ADCC against different solid tumor cell lines. In all cases, profound induction of tumor cell lysis upon application of 293C3-SDIE was observed, and the therapeutic effect of the Fc-optimized mAb clearly exceeded that of its counterpart containing a wild type Fc part. Notably, colony forming unit assays did not reveal any toxicity of 293C3-SDIE at the level of committed hematopoietic progenitor cells. Thus, treatment with 293C3-SDIE constitutes a promising novel strategy for immunotherapy of cancer, in particular considering its ability to preferentially target CSC which is presently under study. Disclosures No relevant conflicts of interest to declare.

Interaction of Human Tumor Cells with Human Platelets and the Coagulation System

1983 ◽  
Vol 50 (03) ◽  
pp. 726-730 ◽  
Author(s):  
Hamid Al-Mondhiry ◽  
Virginia McGarvey ◽  
Kim Leitzel
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
Human Tumor ◽  
Human Platelets ◽  
Factor Vii ◽  
Coagulation System ◽  
Breast Adenocarcinoma ◽  
Activate Factor ◽  
Tumor Cell Lines

SummaryThis paper reports studies on the interaction between human platelets, the plasma coagulation system, and two human tumor cell lines grown in tissue culture: Melanoma and breast adenocarcinoma. The interaction was monitored through the use of 125I- labelled fibrinogen, which measures both thrombin activity generated by cell-plasma interaction and fibrin/fibrinogen binding to platelets and tumor cells. Each tumor cell line activates both the platelets and the coagulation system simultaneously resulting in the generation of thrombin or thrombin-like activity. The melanoma cells activate the coagulation system through “the extrinsic pathway” with a tissue factor-like effect on factor VII, but the breast tumor seems to activate factor X directly. Both tumor cell lines activate platelets to “make available” a platelet- derived procoagulant material necessary for the conversion of prothrombin to thrombin. The tumor-derived procoagulant activity and the platelet aggregating potential of cells do not seem to be inter-related, and they are not specific to malignant cells.

Differential Increases in Glutathione S-Transferase Activities in a Range of Multidrug-Resistant Human Tumor Cell Lines

1989 ◽  
Vol 1 (6) ◽  
pp. 359-365 ◽  
Author(s):  
Richard D. H. Whelan ◽  
Louise K. Hosking ◽  
Alan J. Townsend ◽  
Kenneth H. Cowan ◽  
Bridget T. Hill
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Human Tumor ◽  
Multidrug Resistant ◽  
Tumor Cell Lines ◽  
Glutathione S Transferase ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines

Cytotoxic Activities of Red Algae Collected from Jeju Island Against Four Tumor Cell Lines

2006 ◽  
Vol 11 (3) ◽  
pp. 177-183 ◽  
Author(s):  
Kil-Nam Kim ◽  
Ki-Wan Lee ◽  
Choon-Bok Song ◽  
Chang-Bum Ahn ◽  
You-Jin Jeon
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Red Algae ◽  
Jeju Island ◽  
Cytotoxic Activities ◽  
Tumor Cell Lines

Synthesis and Cytotoxicity of New Mannich Bases of 6-[3-(3,4,5-Trimetoxyphenyl)-2- propenoyl]-2(3H)-Benzoxazolone

2020 ◽  
Vol 17 (4) ◽  
pp. 512-517
Author(s):  
Ognyan Ivanov Petrov ◽  
Yordanka Borisova Ivanova ◽  
Mariana Stefanova Gerova ◽  
Georgi Tsvetanov Momekov
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Biological Activities ◽  
Human Tumor ◽  
Mannich Bases ◽  
In Vitro Cytotoxicity ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines

Background: Chemotherapy is one of the mainstays of cancer treatment, despite the serious side effects of the clinically available anticancer drugs. In recent years increasing attention has been directed towards novel agents with improved efficacy and selectivity. Compounds with chalcone backbone have been reported to possess various biological activities such as anticancer, antimicrobial, anti-inflammatory, analgesic, antioxidant, etc. It was reported that aminomethylation of hydroxy chalcones to the corresponding Mannich bases increased their cytotoxicity. In this context, our interest has been focused on the design and synthesis of the so-called multi-target molecules, containing two or more pharmacophore fragments. Methods: A series of Mannich bases were synthesized by the reaction between 6-[3-(3,4,5- trimethoxyphenyl)-2-propenoyl]-2(3Н)-benzoxazolone, formaldehyde, and a secondary amine. The structures of the compounds were confirmed by elemental analysis, IR and NMR spectra. The new Mannich bases were evaluated for their in vitro cytotoxicity against a panel of human tumor cell lines, including BV-173, SKW-3, K-562, HL-60, HD-MY-Z and MDA-MB-231. The effects of selected compounds on the cellular levels of glutathione (GSH) were determined. Results: The new compounds 4a-e exhibited concentration-dependent cytotoxic effects at micromolar concentrations in MTT-dye reduction assay against a panel of human tumor cell lines, similar to those of starting chalcone 3. The tested agents led to concentration - dependent depletion of cellular GSH levels, whereby the effects of the chalcone prototype 3 and its Mannich base-derivatives were comparable. Conclusion: The highest chemosensitivity to the tested compounds was observed in BV- 173followed by SKW-3 and HL-60 cell lines.

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