Development of a novel potency assay to quantify immune cell-mediated cancer cell killing

Cytotherapy ◽  
2017 ◽  
Vol 19 (5) ◽  
pp. S41
Author(s):  
A. Oumie ◽  
A. Chan ◽  
M. Baradez ◽  
D. Marshall
Keyword(s):  
Cancer Cell ◽  
Immune Cell ◽  
Cell Killing ◽  
Potency Assay

Combination of Oncolytic Adenoviral Therapy with Chemotherapy for Enhanced Breast Cancer Cell Killing – Virotherapy in combination with chemotherapy

2008 ◽  
Vol 68 (S 01) ◽  
Author(s):  
J Jung ◽  
A Nedeljkovic-Kurepa ◽  
B Glover ◽  
DT Curiel ◽  
RK Schmutzler ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cell Killing

Adenosine Analogues as Opposite Modulators of the Cisplatin Resistance of Ovarian Cancer Cells

2019 ◽  
Vol 19 (4) ◽  
pp. 473-486 ◽  
Author(s):  
Katarzyna Bednarska-Szczepaniak ◽  
Damian Krzyżanowski ◽  
Magdalena Klink ◽  
Marek Nowak
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Biology ◽  
Immune Cell ◽  
Immunosuppressive Agents ◽  
Cell Activity ◽  
Ovarian Cancer Cells ◽  
Adenosine Analogues

Background: Adenosine released by cancer cells in high amounts in the tumour microenvironment is one of the main immunosuppressive agents responsible for the escape of cancer cells from immunological control. Blocking adenosine receptors with adenosine analogues and restoring immune cell activity is one of the methods considered to increase the effectiveness of anticancer therapy. However, their direct effects on cancer cell biology remain unclear. Here, we determined the effect of adenosine analogues on the response of cisplatinsensitive and cisplatin-resistant ovarian cancer cells to cisplatin treatment. Methods: The effects of PSB 36, DPCPX, SCH58261, ZM 241385, PSB603 and PSB 36 on cisplatin cytotoxicity were determined against A2780 and A2780cis cell lines. Quantification of the synergism/ antagonism of the compounds cytotoxicity was performed and their effects on the cell cycle, apoptosis/necrosis events and cisplatin incorporation in cancer cells were determined. Results: PSB 36, an A1 receptor antagonist, sensitized cisplatin-resistant ovarian cancer cells to cisplatin from low to high micromolar concentrations. In contrast to PSB 36, the A2AR antagonist ZM 241385 had the opposite effect and reduced the influence of cisplatin on cancer cells, increasing their resistance to cisplatin cytotoxicity, decreasing cisplatin uptake, inhibiting cisplatin-induced cell cycle arrest, and partly restoring mitochondrial and plasma membrane potentials that were disturbed by cisplatin. Conclusion: Adenosine analogues can modulate considerable sensitivity to cisplatin of ovarian cancer cells resistant to cisplatin. The possible direct beneficial or adverse effects of adenosine analogues on cancer cell biology should be considered in the context of supportive chemotherapy for ovarian cancer.

scholarly journals Virotherapy in Germany—Recent Activities in Virus Engineering, Preclinical Development, and Clinical Studies

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1420
Author(s):  
Dirk M. Nettelbeck ◽  
Mathias F. Leber ◽  
Jennifer Altomonte ◽  
Assia Angelova ◽  
Julia Beil ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Targeted Delivery ◽  
Viral Vector ◽  
Checkpoint Inhibitors ◽  
Therapeutic Proteins ◽  
Cancer Therapeutics ◽  
Cell Killing ◽  
Oncolytic Viruses ◽  
Preclinical Research ◽  
Research Activities

Virotherapy research involves the development, exploration, and application of oncolytic viruses that combine direct killing of cancer cells by viral infection, replication, and spread (oncolysis) with indirect killing by induction of anti-tumor immune responses. Oncolytic viruses can also be engineered to genetically deliver therapeutic proteins for direct or indirect cancer cell killing. In this review—as part of the special edition on “State-of-the-Art Viral Vector Gene Therapy in Germany”—the German community of virotherapists provides an overview of their recent research activities that cover endeavors from screening and engineering viruses as oncolytic cancer therapeutics to their clinical translation in investigator-initiated and sponsored multi-center trials. Preclinical research explores multiple viral platforms, including new isolates, serotypes, or fitness mutants, and pursues unique approaches to engineer them towards increased safety, shielded or targeted delivery, selective or enhanced replication, improved immune activation, delivery of therapeutic proteins or RNA, and redirecting antiviral immunity for cancer cell killing. Moreover, several oncolytic virus-based combination therapies are under investigation. Clinical trials in Germany explore the safety and potency of virotherapeutics based on parvo-, vaccinia, herpes, measles, reo-, adeno-, vesicular stomatitis, and coxsackie viruses, including viruses encoding therapeutic proteins or combinations with immune checkpoint inhibitors. These research advances represent exciting vantage points for future endeavors of the German virotherapy community collectively aimed at the implementation of effective virotherapeutics in clinical oncology.

600 In vitro anticancer and immunomodulatory activities of NBT-167, a dimer of resveratrol

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A635-A635
Author(s):  
Jeffrey Zhang ◽  
Everett Henry ◽  
L Harris Zhang ◽  
Wanying Zhang
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Immune Cells ◽  
Cell Killing ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Raw264.7 Macrophages

BackgroundResveratrol (3,4’,5-trihydroxystilbene), a stilbenoid isolated from many species of plants, is widely known for its antioxidative, anti-inflammatory, immunomodulatory and anticancer activities. Recently, novel resveratrol oligomers have been isolated from various plants; their diverse structures are characterized by the polymerization of two or more resveratrol units. Little is known regarding the anticancer and immunomodulating activities of these oligomers. In this study, we designed in vitro models to compare resveratrol side by side with its natural dimer NBT-167 for their anticancer and immunological activities.MethodsWe isolated resveratrol and its dimer (NBT-167) from plants. The potency of the compounds was compared side by side using cancer cell survival assays and immunological assays with various types of human cells including cancer cell lines, PBMCs and enriched NK, gamma delta T cells, THP-1 monocytic cells, HL-60 promyelocytic leukemia cells as well as mouse RAW264.7 macrophages.ResultsNBT-167 was found to be more potent than resveratrol in inhibiting growth of various cancer cells and modulation of cytokine production from anti-IgM, LPS, PHA or SEB stimulated PBMC. Both compounds similarly enhanced IL-2 stimulated NK and gamma delta T cell killing activity against K562 cells and modulated nitric oxide production from LPS/IFN-g induced RAW264.7 macrophages and phagocytotic activity of HL-60 cells. NBT-167 was slightly more potently than resveratrol in inhibiting chemotaxis of HL-60 cells and blocking cell cycle of THP-1 and HL-60 cells at G1/S transition. In addition, NBT-167, but not resveratrol, could increase IL-2 production and T cell proliferation stimulated with anti-CD3 and anti-CD28 and synergize with anti-PD-1 antibody to increase IL-2 and IFN-gamma production in co-culture of allotypic T cells and dendric cells (MLR).ConclusionsOur data showed that NBT-167, a dimer of resveratrol, had anticancer and immunomodulatory activities such as modulation of expression of cytokines in immune cells and induction of cancer cell-killing activities of NK and gamma delta T cells. Generally, NBT-167 appeared to have higher activities than resveratrol in modulating immune cells and inhibiting cancer cells. NBT-167 could be a promising cancer immunotherapeutic agent targeting both cancer cells and immune cells.

scholarly journals Combined inhibition of glycolysis and AMPK induces synergistic breast cancer cell killing

2015 ◽  
Vol 151 (3) ◽  
pp. 529-539 ◽  
Author(s):  
Yong Wu ◽  
Marianna Sarkissyan ◽  
Eva Mcghee ◽  
Sangkyu Lee ◽  
Jaydutt V. Vadgama
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cell Killing ◽  
Inhibition Of Glycolysis

Pre-clinical models of cellular therapy combined with cytokines demonstrate in vitro and in vivo ovarian cancer cell killing

2012 ◽  
Vol 125 ◽  
pp. S45
Author(s):  
S. Ingersoll ◽  
S. Ahmad ◽  
G. Stoltzfus ◽  
M. Merchant ◽  
A. Ahmed ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cell ◽  
Cellular Therapy ◽  
Ovarian Cancer Cell ◽  
Cell Killing ◽  
Clinical Models

The Involvement of Oxy-Radicals in Cancer Cell Killing and Growth

1993 ◽  
pp. 218-225
Author(s):  
T. Galeotti ◽  
S. Borrello ◽  
M. E. De Leo ◽  
L. Masotti
Keyword(s):  
Cancer Cell ◽  
Cell Killing

scholarly journals Search for receptors in immune cells that bind cancer cell antigens and their activation in silent cases

2019 ◽  
Author(s):  
Wenfa Ng
Keyword(s):  
Immune System ◽  
Amino Acid ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Immune Cells ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Host Cells ◽  
Immune Receptor

The immune checkpoint plays an important role in keeping immune cells in check for protecting tissues and organs from attack by the body’s own immune system. Similar concepts also apply in how cancer cells managed to fool immune cells through the surface display of particular antigens that mimic those exhibited by normal body cells. Specifically, cancer cells display antigens that bind to receptors on immune cells that subsequently prevent an attack on the cancer cells. Such binding between cancer antigens and immune cell receptors can be prevented through the use of checkpoint inhibitors antibodies specific for particular receptors on immune cells; thereby, unleashing immune cells to mount an immune response against cancer cells. While demonstrating good remissions in many patients where tumours shrunk substantially after administration of checkpoint inhibitors, cases exist where an overactivated immune system cause harm to organs and tissues culminating in multiple organ failure. Analysis of such toxicity effects of checkpoint inhibitors revealed that generic nature of targeted immune receptor plays a pivotal role in determining extent of side effects. Specifically, if the target immune receptor participates in checkpoints that prevent immune cells from attacking host cells, unleashing such receptors in cancer therapy may have untoward effects on patient’s health. Hence, the goal should be the selection of immune cell receptor specific to cancer cell antigens and which does not bind antigens or ligands displayed by the body’s cells. Such receptors would provide ideal targets for the development of checkpoint inhibitor antibodies for unleashing immune cells against cancer cells. To search for non-generic receptors that bind cancer cell antigens only, a combined computational and experimental approach could be used where ensemble of surface antigens on cancer cells and available receptors on immune cells could be profiled by biochemical assays. Downstream purification of ligands and receptors would provide for both structural elucidation and amino acid sequencing useful for bioinformatic search of homologous sequences. Knowledge of the antigens’ and receptors’ structures and amino acid sequence would subsequently serve as inputs to computational algorithms that models molecular docking events between receptor and antigen. This paves the way for heterologous expression of putative ligand and receptor in cell lines cultured in co-culture format for assessing binding between ligand and receptor, and more importantly, its physiological effects. Ability of immune receptor to bind to ligands on normal cells could also be assessed. Similar co-culture studies could be conducted with cancer cells and different immune cell types to check for reproducibility of observed effect in cell lines. Finally, antibodies could be raised for candidate receptors whose inhibition would not result in systemic attack of immune cells on host cells.

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