scholarly journals Bispecific Antibodies for IFN-β Delivery to ErbB2+ Tumors

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1915
Author(s):  
Vladislav S. Rybchenko ◽  
Anna A. Panina ◽  
Teimur K. Aliev ◽  
Olga N. Solopova ◽  
Dmitry S. Balabashin ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Targeted Delivery ◽  
Interferon Beta ◽  
Bispecific Antibody ◽  
Chimeric Antibody ◽  
Tumor Cell Lines ◽  
Erbb2 Receptor ◽  
Human Igg1 ◽  
Covalent Complex ◽  
Ht29 Cell Line

The main aim of our work was to create a full-length bispecific antibody (BsAb) as a vehicle for the targeted delivery of interferon-beta (IFN-β) to ErbB2+ tumor cells in the form of non-covalent complex of BsAb and IFN-β. Such a construct is a CrossMab-type BsAb, consisting of an ErbB2-recognizing trastuzumab moiety, a part of chimeric antibody to IFN-β, and human IgG1 Fc domain carrying knob-into-hole amino acid substitutions necessary for the proper assembly of bispecific molecules. The IFN-β- recognizing arm of BsAb not only forms a complex with the cytokine but neutralizes its activity, thus providing a mechanism to avoid the side effects of the systemic action of IFN-β by blocking IFN-β Interaction with cell receptors in the process of cytokine delivery to tumor sites. Enzyme sandwich immunoassay confirmed the ability of BsAb to bind to human IFN-β comparable to that of the parental chimeric mAb. The BsAb binds to the recombinant ErbB2 receptor, as well as to lysates of ErbB2+ tumor cell lines. The inhibition of the antiproliferative effect of IFN-β by BsAb (IC50 = 49,3 µg/mL) was demonstrated on the HT29 cell line. It can be proposed that the BsAb obtained can serve as a component of the immunocytokine complex for the delivery of IFN-β to ErbB2-associated tumor cells.

scholarly journals Recombinant Bispecific Antibodies to the Human ErbB2 Receptor and Interferon-Beta

Acta Naturae ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 95-104
Author(s):  
A. A. Panina ◽  
V. S. Rybchenko ◽  
O. N. Solopova ◽  
D. S. Balabashin ◽  
S. A. Yakimov ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Interferon Beta ◽  
Bispecific Antibody ◽  
Type I Interferons ◽  
Bispecific Antibodies ◽  
Type I ◽  
Systemic Action ◽  
Erbb2 Receptor ◽  
The Moment ◽  
The One

The development of and research into new therapies that can selectively and effectively destroy tumor cells that overexpress the ErbB2 receptor is apressing task. Recently, research into the use of type I interferons in the treatment of cancer has intensified. Cytokine therapy is aimed at activating the cells of the immune system to fight tumors, but it has drawbacks that limit its use because of a number of side effectsthe severity of which varies depending on the dosage and type of used cytokine. At the moment, a number of studies are being conducted regarding the use of IFNin oncology. The studies areaimed at mitigating the systemic action of this cytokine. The immunocytokine complex made of a bispecific antibody against the ErbB2 receptor and recombinant IFNdeveloped in this study underlies themechanism meant to avoid the systemic action of this cytokine. Part of this study focuses on the development of full-length antibodies that bind to the ErbB2 receptor on the one hand, and bind and neutralize IFN, on the other hand, which allows us to consider the antibodies as a means of cytokine delivery to tumor cells.

scholarly journals Recombinant Bispecific Antibodies to the Human ErbB2 Receptor and Interferon-Beta

Acta Naturae ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 95-104
Author(s):  
A. A. Panina ◽  
V. S. Rybchenko ◽  
O. N. Solopova ◽  
D. S. Balabashin ◽  
S. A. Yakimov ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Interferon Beta ◽  
Bispecific Antibody ◽  
Type I Interferons ◽  
Bispecific Antibodies ◽  
Type I ◽  
Systemic Action ◽  
Erbb2 Receptor ◽  
The Moment ◽  
The One

The development of and research into new therapies that can selectively and effectively destroy tumor cells that overexpress the ErbB2 receptor is apressing task. Recently, research into the use of type I interferons in the treatment of cancer has intensified. Cytokine therapy is aimed at activating the cells of the immune system to fight tumors, but it has drawbacks that limit its use because of a number of side effectsthe severity of which varies depending on the dosage and type of used cytokine. At the moment, a number of studies are being conducted regarding the use of IFNin oncology. The studies areaimed at mitigating the systemic action of this cytokine. The immunocytokine complex made of a bispecific antibody against the ErbB2 receptor and recombinant IFNdeveloped in this study underlies themechanism meant to avoid the systemic action of this cytokine. Part of this study focuses on the development of full-length antibodies that bind to the ErbB2 receptor on the one hand, and bind and neutralize IFN, on the other hand, which allows us to consider the antibodies as a means of cytokine delivery to tumor cells.

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.

Nano Technological Approach for Anti-Tumor Therapy: Opportunities and Challenges

2020 ◽  
Vol 10 ◽  
Author(s):  
Krishna Champaneria ◽  
Prajesh Prajapati
Keyword(s):  
Adverse Effects ◽  
Tumor Cells ◽  
Targeted Delivery ◽  
Blood Circulation ◽  
Review Paper ◽  
Tumor Therapy ◽  
Conventional Chemotherapy ◽  
Targeting Delivery ◽  
Tumor Accumulation ◽  
Work Done

Cancer is one of the reason for mortality and its individual and collective impact is substantial. Conventional chemotherapy utilizes drugs that can destroy Tumor cells effectively. But these agents destroy healthy cells along with the tumor cells, leading to many adverse effects which include hypersensitivity reactions, nephrotoxicity, and neurotoxicity. To minimize the adverse effects, various drug delivery systems (DDSs) has been developed. Among them, nanoparticles are attractive platforms for it. So this review paper explores the recent work done on targeted delivery, enhancing tumor accumulation and longer blood circulation using more effective biomaterial that will enhance the properties of nanoparticles. Moreover, various target-specific delivery of drugs like antibody-targeted, targeting delivery through angiogenesis, mitochondria, CD44 receptor are also explained.

scholarly journals Bone tumor-targeted delivery of theranostic 195mPt-bisphosphonate complexes promotes killing of metastatic tumor cells

2020 ◽  
pp. 100088
Author(s):  
Robin A. Nadar ◽  
Gerben M. Franssen ◽  
Natasja W.M. Van Dijk ◽  
Karlijn Codee-van der Schilden ◽  
Mirjam de Weijert ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Bone Tumor ◽  
Targeted Delivery ◽  
Metastatic Tumor

scholarly journals Enhanced transfection efficiency and targeted delivery of self-assembling h-R3-dendriplexes in EGFR-overexpressing tumor cells

Oncotarget ◽  
2015 ◽  
Vol 6 (28) ◽  
pp. 26177-26191 ◽  
Author(s):  
Jun Li ◽  
Shengnan Li ◽  
Songyun Xia ◽  
Jinfeng Feng ◽  
Xuedi Zhang ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Targeted Delivery ◽  
Transfection Efficiency ◽  
Self Assembling

scholarly journals A Nuclear-Directed Ribonuclease Variant Targets Cancer Stem Cells and Inhibits Migration and Invasion of Breast Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4350
Author(s):  
Jessica Castro ◽  
Giusy Tornillo ◽  
Gerardo Ceada ◽  
Beatriz Ramos-Neble ◽  
Marlon Bravo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cell Lines ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Tumor Cell Lines

Despite the significant advances in cancer research made in recent years, this disease remains one of the leading causes of death worldwide. In part, this is due to the fact that after therapy, a subpopulation of self-renewing tumor cells can survive and promote cancer relapse, resistance to therapies and metastasis. Targeting these cancer stem cells (CSCs) is therefore essential to improve the clinical outcome of cancer patients. In this sense, multi-targeted drugs may be promising agents targeting CSC-associated multifocal effects. We have previously constructed different human pancreatic ribonuclease (RNase) variants that are cytotoxic for tumor cells due to a non-classical nuclear localization signal introduced in their sequence. These cytotoxic RNases affect the expression of multiple genes involved in deregulated metabolic and signaling pathways in cancer cells and are highly cytotoxic for multidrug-resistant tumor cell lines. Here, we show that these cytotoxic nuclear-directed RNases are highly selective for tumor cell lines grown in 3D, inhibit CSCs’ development and diminish the self-renewal capacity of the CSCs population. Moreover, these human RNase variants reduce the migration and invasiveness of highly invasive breast cancer cells and downregulate N-cadherin expression.

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