Antiproliferative and Antitumor Activity of the 2-Cyanoaziridine Compound Imexon on Tumor Cell Lines and Fresh Tumor Cells In Vitro

1992 ◽  
Vol 84 (16) ◽  
pp. 1238-1244 ◽  
Author(s):  
E. M. Hersh ◽  
C. R. Gschwind ◽  
C. W. Taylor ◽  
R. T. Dorr ◽  
R. Taetle ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
Tumor Cell Lines

scholarly journals Breast Tumor Cell Lines From Pleural Effusions2

1974 ◽  
Vol 53 (3) ◽  
pp. 661-674 ◽  
Author(s):  
R. Cailleau ◽  
R. Young ◽  
M. Olivé ◽  
W. J. Reeves
Keyword(s):  
Chromosome Number ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
Breast Tumor ◽  
Tumor Cell Lines ◽  
Breast Cancer Patients ◽  
Pleural Effusions ◽  
Epithelial Tumor

Summary During 1973, 4 new epithelial tumor cell lines were isolated from pleural effusions from breast cancer patients. We describe 3 of these lines: MDA-MB-134, with a mean chromosome number of 43; MDA-MB-175, with a mean chromosome number of 49; and MDA-MB-231, with a mean chromosome number between 65 and 69. We isolated the same cell type from 4 of 10 effusions from MDA-MB-134 and from 6 of 8 effusions from MDA-MB-175. We found that pleural effusions as a source of breast tumor cells to be cultured and studied in vitro have the following advantages: 1) large amounts of material and the possibility of obtaining sequential samples from the same patient; 2) high viability of tumor cells; 3) scarcity or absence of fibroblasts; and 4) the possibility of separating the tumor cells from other “contaminating” cell types by differences in their speed or degree of attachment to the flask. All lines from different patients differed, as seen grossly and microscopically. All lines from sequential pleural effusions from the same patient were apparently alike. No viruses or mycoplasmas were detected in any line.

scholarly journals Antitumor Activity In Vitro Provided by N-Alkyl-Nitroimidazole Compounds

2020 ◽  
Vol 14 (1) ◽  
pp. 45-48
Author(s):  
Janny A. Villa-Pulgarin ◽  
Constain H. Salamanca ◽  
Jose Oñate-Garzón ◽  
Ruben E Varela-M
Keyword(s):  
Antitumor Activity ◽  
Tumor Cell ◽  
Cell Lines ◽  
Alkyl Chain ◽  
Imidazole Ring ◽  
Antitumoral Activity ◽  
Lung Cells ◽  
Tumor Cell Lines ◽  
A549 Lung

Background: Cancer is one of the most common diseases in the world, with over 18 million new cases estimated in 2018. Many of the drugs used for cancer can have significant adverse effects and variable effectiveness. Nitroimidazoles are prodrugs that usually have shown antimicrobial activity specifically antiparasitic. However, its antitumor activity in vitro has barely been explored. Objective: The aim of this study is to determine the influence of the length of the substituted N-alkyl chain in the imidazole ring on the antitumor activity in vitro. Methods: Four nitroimidazoles were obtained by chemical synthesis varying the length of the substituted N-alkyl chain from methyl to butyl. The antitumor activity of N-alkyl-nitroimidazoles was evaluated by MTT assay employing two tumor cell lines (MDA-MB231 and A549). Results: In this study, it was reported that N-alkyl nitroimidazoles exhibited an LC50 as low as 16.7 µM in breast tumor cells MDA-MB231 while in normal Vero kidney cells, the LC50 was around 30 µM. It was also reported that the length of the substituted N-Alkyl chain in the imidazole ring affects the antitumoral activity in A549 lung cells. Conclusion: Increasing the length of the substituted N-Alkyl chain in the imidazole ring decreased the antitumor activity against only A549 cancer cells. N-alkyl nitroimidazoles exhibited considerable selectivity towards tumor cell lines.

Synthesis and biological activity of (S)-2′-fluorodaunorubicin

1988 ◽  
Vol 66 (1) ◽  
pp. 187-190 ◽  
Author(s):  
Hans H. Baer ◽  
Lisa Siemsen
Keyword(s):  
Biological Activity ◽  
Antitumor Activity ◽  
Tumor Cell ◽  
Cell Lines ◽  
Title Compound ◽  
Free Sugar ◽  
Tumor Cell Lines ◽  
Murine Leukemia

Methyl 3-amino-2,3,6-trideoxy-2-fluoro-β-L-galactopyranoside was hydrolyzed to the free sugar, (S)-2-fluorodaunosamine hydrochloride, which was converted into the α,β-1,4-di-O-acetyl-N-trifluoroacetyl derivative and thence into the corresponding glycosyl bromide. The latter was condensed with daunomycinone, and the product was deprotected to give the title compound. The fluoroanthracycline displayed significant cytotoxicity against a number of tumor cell lines in vitro. Antitumor activity against L1210 murine leukemia in vivo was lower than that of the parent daunorubicin, but toxicity appeared to be reduced.

In vivo and in vitro antitumor activity of oxaliplatin in combination with cetuximab in human colorectal tumor cell lines expressing different level of EGFR

2005 ◽  
Vol 57 (6) ◽  
pp. 709-718 ◽  
Author(s):  
Diane Balin-Gauthier ◽  
Jean-Pierre Delord ◽  
Philippe Rochaix ◽  
Valérie Mallard ◽  
Fabienne Thomas ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Cell ◽  
Cell Lines ◽  
Colorectal Tumor ◽  
Tumor Cell Lines ◽  
Colorectal Tumor Cell

High affinity Fc receptor binding and potent induction of antibody-dependent cellular cytotoxicity (ADCC) in vitro by anti-epidermal growth factor receptor antibody cetuximab

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3041-3041 ◽  
Author(s):  
X. Kang ◽  
D. Patel ◽  
S. Ng ◽  
M. Melchior ◽  
D. Ludwig ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Nk Cells ◽  
Tumor Cells ◽  
Cell Lines ◽  
Growth Factor Receptor ◽  
Tumor Cell Lines ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Effector Cells ◽  
Epidermal Growth

3041 Background: Cetuximab is an IgG1 monoclonal antibody specific for human epidermal growth factor receptor (EGFR). Cetuximab acts as a functional antagonist by blocking ligand (EGF and TGFa) binding to EGFR and, therefore, inhibits EGFR activation and downstream signaling in tumor cells. Methods: In the present study, we analyzed the binding activity of cetuximab to human Fc receptors and tested whether cetuximab can elicit antibody-dependent cellular cytotoxicity (ADCC) in vitro using tumor cell lines expressing various levels of EGFR. Results: Cetuximab bound to human FcRI and FcRIII with high affinity (EC50 of 0.13 nM and 6 nM, respectively), whereas an aglycosylated form of cetuximab or an IgG2 antibody to EGFR (panitumumab) did not bind to FcRI and FcRIII. A panel of head and neck, colon, and breast tumor cell lines were tested for cetuximab-mediated ADCC using human peripheral blood mononuclear cells (PBMC) from normal donors as effector cells. We found that cetuximab-induced ADCC to these tumor cell lines ranging from 20–90% specific killing. Interestingly, the extent of ADCC induced by cetuximab correlated with the level of EGFR expression on cell surface. The aglycosylated form of cetuximab or panitumumab, did not elicit ADCC of EGFR expressing tumor cells, even though cetuximab and panitumumab bind to EGFR with similar affinity (Kd=87 pM and 83 pM, respectively). To identify the immune cell population responsible for ADCC, NK cells were isolated from PBMC and tested in an ADCC assay. Purified NK cells elicited high levels of specific killing of cetuximab bound tumor cells, suggesting that NK cells are one of effector cell populations in human PBMCs responsible for the observed ADCC activity. Conclusions: Thus, cetuximab can effectively link effector cells to EGFR expressing tumor cells and mediate potent ADCC against EGFR-expressing human tumors. [Table: see text]

scholarly journals Human Placental CD34 +-Derived Natural Killer Cells with High Affinity and Cleavage Resistant CD16 (CYNK-101) in Combination with Daratumumab for Immunotherapy Against CD38 Expressing Hematological Malignancies

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2773-2773
Author(s):  
Irene Raitman ◽  
Joseph Gleason ◽  
Salvatore Rotondo ◽  
Shuyang He ◽  
Valentina Rousseva ◽  
...  
Keyword(s):  
B Cells ◽  
Tumor Cell ◽  
Nk Cells ◽  
Tumor Cells ◽  
Cell Lines ◽  
Xenograft Model ◽  
Tumor Cell Lines ◽  
Publicly Traded

Abstract Natural Killer (NK) cells are key mediators of antibody dependent cellular cytotoxicity (ADCC) via the CD16 Fc receptor. NK cellular therapies can effectively be targeted to tumor antigens when combined with tumor specific antibodies. Celularity Inc. is developing human placental CD34 +-derived, cryopreserved, off-the-shelf, allogenic NK cells (CYNK-101) with a high IgG binding affinity and proteinase cleavage resistant CD16 variant (CD16VP) for cancer treatment. We hypothesize that expressing CD16VP augments anti-tumor ADCC activity. Reported here are the in vitro and in vivo results of evaluating CYNK-101 cytotoxicity against CD38 expressing multiple myeloma (MM) and lymphoma tumor cell lines when in combination with daratumumab, an anti-CD38 monoclonal antibody. Human placental CD34 + cells were transduced with lentivirus expressing CD16VP and cultured in the presence of cytokines to generate CYNK-101 cells. The in vitro cytotoxic activity of CYNK-101 against CD38 + MM (MOLP-8, LP-1, MM.1S) and lymphoma (Daudi) tumor cell lines, and normal B-cells was assessed in combination with daratumumab via flow cytometry based ADCC assays and cytokine secretion was assessed via multiplex Luminex analysis. In vivo ADCC activity of CYNK-101 was assessed using a disseminated B-cell lymphoma xenograft model in B-NDG-hIL15 mice. B-NDG-hIL15 mice lack T, B, and NK cells and are transgenic for human IL-15 to support CYNK-101 persistence and maturation. Luciferase expressing Daudi cells (3×10 6) were intravenously (IV) injected on Day 0 three days after preconditioning with a myeloablative dose of busulfan to allow for better tumor cell engraftment. CYNK-101 cells (1x10 7) and/or daratumumab (0.05 mg/kg) were IV injected on Days 7, 14 and 21. Tumor burden was assessed weekly by bioluminescence imaging (BLI) and the mice were followed for assessment of their survival (n=5 mice per group). In vitro ADCC studies indicate enhanced cytolysis of CYNK-101 in combination with daratumumab against both MM and lymphoma tumor cells compared to that of IgG control. At 24h at the effector to target (E:T) ratio of 5:1, CYNK-101 (n=5 donors) demonstrated a cytolysis of 87.6 ± 6.3% with daratumumab vs. 37.3 ± 9.5% with IgG control against MOLP-8 (p<0.001), 73.9 ± 2.5% vs. 32.1 ± 7.2% against LP-1 (p<0.001), 77.2 ± 11.5% vs. 67.4 ± 10.7% against MM.1S (p<0.001), and 54.7 ± 24.0% vs. 4.3 ± 2.6% against Daudi (p<0.01) tumor cells. Secretion of GM-CSF, IFN-γ, and TNF-α was increased in CYNK-101 co-cultured with the tumor cell lines in the presence of daratumumab for 24h (n=5 donors, p<0.05). When cocultured with mixed LP-1 and CD38 + normal B-cells, CYNK-101 in combination with daratumumab displayed specific cytotoxicity against LP-1, while sparing CD38 + normal B-cells even at an E:T ratio up to 100:1, demonstrating that CYNK-101 can distinguish CD38 + tumor cells from CD38 + normal cells. Additionally, despite expression of CD38 on CYNK-101 there was no NK fratricide observed when CYNK-101 were in combination with daratumumab. In vivo studies in the lymphoma xenograft model revealed a significant decrease in tumor burden as evidenced from bioluminescence imaging at day 28 (1 week after last CYNK-101 injection) for mice that received CYNK-101 in combination with daratumumab compared to vehicle control (p<0.001), CYNK-101 (p<0.05) and daratumumab (p<0.05). Furthermore, CYNK-101 in combination with daratumumab demonstrated an enhanced survival benefit with a median survival of 35 days versus a median survival of 28 days for the vehicle treated group (p<0.005). In summary, our results demonstrate enhanced in vitro and in vivo ADCC activities of CYNK-101 in combination with daratumumab against CD38 + hematological tumors and warrant further development of this combination therapy for these cancers. Disclosures Raitman: Celularity Inc.: Current Employment, Current equity holder in publicly-traded company. Gleason: Celularity Inc.: Current Employment, Current equity holder in publicly-traded company. Rotondo: Celularity Inc.: Current Employment, Current equity holder in publicly-traded company. He: Celularity Inc.: Current Employment, Current equity holder in publicly-traded company. Rousseva: Celularity Inc.: Current Employment, Current equity holder in publicly-traded company. Guo: Celularity Inc.: Current Employment, Current equity holder in publicly-traded company. Rana: Celularity Inc.: Current Employment, Current equity holder in publicly-traded company. van der Touw: Celularity Inc.: Current Employment, Current equity holder in publicly-traded company. Ye: Celularity Inc.: Current Employment, Current equity holder in publicly-traded company. Kang: Celularity Inc.: Current Employment, Current equity holder in publicly-traded company. Hariri: Celularity Inc.: Current Employment, Current equity holder in publicly-traded company. Zhang: Celularity Inc.: Current equity holder in publicly-traded company, Ended employment in the past 24 months.

scholarly journals Nanobody Armed T Cells Endow CAR-T Cells the Ability to Against Lymphoma Cells

2021 ◽  
Author(s):  
Hongxia Wang ◽  
Liyan Wang ◽  
Yanning Li ◽  
Guangqi Li ◽  
Xiaochun Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
Phage Display Library ◽  
Target Cells ◽  
Tumor Cell Lines ◽  
Car T Cells ◽  
Car T

Abstract BackgroundTaking advantages of nanobody (Nb) in immunotherapy, here we investigate the cytotoxicity of Nb based Chimeric antigen receptor T cells (Nb CAR-T) against Lymphoma cells.MethodsCD19 Nb CAR-T, CD20 Nb CAR-T, and Bispecific Nb CAR-T cells were generated by panning anti-human CD19, CD20 specific nanobodies sequences from naive phage display library, then integrating Nb genes with lentiviral cassette that included other CARs elements, and finally transducing T cells that were expanded under optimization system with above prepared CARs lentiviruses. Prepared Nb CAR-T cells were co-cultured with tumor cell lines or primary tumor cells for 24 hours or 5 days to evaluate the biological function. ResultsObtained several Nb sequences specific to CD19 and CD20. Optimized culture conditions of T cells that expand 87.5 folds after 7 days of activation. Generated Nb CAR-T cells that could recognize Burkitt lymphoma cell lines (Raji and Daudi), induce activation, proliferation, and therefore kill target cells specifically. Furthermore, same results were also obtained from patient samples with cytotoxicity about 60%. ConclusionsOur study demonstrated that nanobody based single and bispecific CAR-T cells have certain killing ability against both tumor cell lines and patient-derived tumor cells in vitro.

Bbr 2778, an Aza-anthracenedione Endowed with Preclinical Anticancer Activity and Lack of Delayed Cardiotoxicity

2001 ◽  
Vol 87 (6) ◽  
pp. 407-416 ◽  
Author(s):  
Gino Beggiolin ◽  
Luca Crippa ◽  
Ernesto Menta ◽  
Carla Manzotti ◽  
Ennio Cavalletti ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Cell ◽  
Cell Lines ◽  
Dose Range ◽  
Human Tumor ◽  
Tumor Cell Lines ◽  
In Vivo Models ◽  
Interesting Compound

With the aim to provide second-generation anthracenedione analogues endowed with reduced side effects and a wider spectrum of action than mitoxantrone and doxorubicin, a large number of new molecules bearing nitrogen atoms in the chromophore was synthesized and screened in vitro and in vivo. From this screening, BBR 2778 (6,9-bis[(2-aminoethyl)amino] benzo[g]isoquinoline-5,10-dione dimaleate) emerged as the most interesting compound. BBR 2778 was tested in vitro on several murine and human tumor cell lines and showed cytotoxic potency lower than that of mitoxantrone and doxorubicin. BBR 2778 was more cytotoxic in leukemia and lymphoma cell lines than in solid tumor cell lines. Although against in vivo models BBR 2778 was less potent than mitoxantrone and doxorubicin, its antitumor activity was equal or superior (in certain tumor models) to that of the above standard compounds. In particular, BBR 2778 was curative against L1210 murine leukemia and YC-8 murine lymphoma. Moreover, it showed an antitumor activity comparable to that of mitoxantrone and doxorubicin on solid tumors. No cardiotoxic effect of BBR 2778 in animals not pretreated with anthracyclines was observed compared to standards. In light of its spectrum of activity and marked efficacy against lymphomas and leukemias over a wide dose range, together with its lack of delayed cardiotoxicity, BBR 2778 has been entered in clinical studies.

Placenta Derived Adherent Cells (PDACs) Suppress Tumor Cells of Diverse Origin.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4813-4813
Author(s):  
Ryhor Harbacheuski ◽  
Casper Paludan ◽  
Rose Ann Murray ◽  
Megan Mendillo ◽  
Jorge Soler ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
Colon Adenocarcinoma ◽  
Annexin V ◽  
Myelogenous Leukemia ◽  
Adherent Cells ◽  
Tumor Cell Lines ◽  
Monocyte Chemoattractant Protein 1

Abstract The placenta is a readily available and ethically non-controversial source of large amounts of therapeutic stem cells. We isolated adherent cells from the Umbilical Cord (UC) and the Amnion Chorion (AC) of term placentas. These Placenta Derived Adherent Cells (PDACs) displayed a cell surface phenotype of CD29+, CD44+, CD73+, CD90+, CD105+, CD200+, CD34−, and constitutively secreted IL-6, IL-8 and Monocyte Chemoattractant protein-1 (MCP-1). PDACs demonstrated in vitro pluripotency and suppressed T cell proliferation in both the allogeneic mixed leukocyte reaction, and the autologous EBV regression assay. Because progenitor cells have been described to inhibit tumor growth in some systems, the role of PDACs in tumor suppression was investigated. EBV transformed tumor cells were cultured either alone, or with AC or UC PDACs. After 6 days, live (7-AAD− Annexin-V−) tumor cells were counted on a flow cytometer. Free growing tumor cells numbered 40,000. When tumor cells were co-cultured with AC or UC PDACs, the growth was suppressed to 10,000 cells, a suppression of 75%. We designed and tested a panel of tumor cell lines that included retinoblastoma (RB), histiocytic lymphoma (HL), chronic myelogenous leukemia (CML), and colon adenocarcinoma (CAC). The tissue origin of the selected tumor cell lines included neuronal tissue (retinoblastoma), epithelium (carcinomas) and the hematopoietic lineage (lymphomas and CML). Co-culture experiments showed that the growth of all tumor lines was suppressed more than 40%. When a transwell was introduced separating PDACs and tumor cells, contact dependency of suppression was 12% for HL, 22% for CML, 42% for CAC, and 51% for EBV transformed tumor cells. These results indicate that PDACs may have therapeutic value with respect to certain cancers.

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