scholarly journals Humanized animals as models of experimental oncology (review)

2022 ◽  
Vol 20 (6) ◽  
pp. 141-150
Author(s):  
O. I. Kit ◽  
G. V. Zhukova ◽  
A. Yu. Maksimov ◽  
A. S. Goncharova ◽  
E. Yu. Zlatnik ◽  
...  
Keyword(s):  
Immune Cells ◽  
Malignant Tumors ◽  
Experimental Models ◽  
Therapeutic Effects ◽  
Hematopoietic Stem ◽  
Oncology Review ◽  
Human Immune ◽  
Human Malignant Tumors ◽  
Advanced Tool ◽  
Newborn Animals

The humanization of immunodeficient animals allows us to study the growth of xenografts of human malignant tumors and their response to therapeutic effects, taking into account processes in the immune system and tumor zone, which have a significant impact on oncogenesis and the effectiveness of antitumor therapy. Such experimental models are currently considered as the most advanced tool in the development of personalized antitumor treatment. The lines of immunodeficient animals most commonly used for the transplantation of mature and stem human immune cells have been characterized. The main sources of human immune cells when implementing the hu-pbl and hu-cd34+ models, as well as the blt model (as an option to the cd34+ model) are described. The basic procedures necessary for reproducing each model, their modification in adult and newborn animals are outlined as well as the parameters of immunosuppressive radiation exposure, preceding the transplantation of human hematopoietic stem cells. The main results of the humanization of immunodeficient animals and examples of the use of these models for the purposes of fundamental and clinical oncology are described. The main problems of this direction are discussed. The review is based on an analysis of the literature presented in the scopus, web of science, medline, risc and others databases over the past 7 years (over 80 % of literature sources, with more than over 50 % of studies published over the last 3 years).

Current Research and Use of Mesenchymal Stem Cells in the Therapy of Autoimmune Diseases

2019 ◽  
Vol 14 (7) ◽  
pp. 579-582 ◽  
Author(s):  
Youdong Chen ◽  
Qian Yu ◽  
Yifan Hu ◽  
Yuling Shi
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Autoimmune Diseases ◽  
Immune Cells ◽  
Therapeutic Effectiveness ◽  
Therapeutic Effects ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Novel Treatment ◽  
Body Tissues

: Mesenchymal Stem Cells (MSCs) represent a heterogeneous group of self-renewal, multipotent non-hematopoietic stem cells, which display profound immunomodulatory functions and promising therapeutic effects. Autoimmune diseases, which result from an aberrant immune response to selfantigens, can be detrimental to nearly all body tissues. With the advance in developing a novel treatment, including biological agents, it is still impossible to cure autoimmune disorders. Recent studies demonstrate the remarkable therapeutic effectiveness of MSCs towards a wide array of autoimmune diseases. In this review, the immunomodulatory influence of MSCs over immune cells and the application of MSCs transplantation in treating autoimmune diseases are highlighted.

Activation of human immune cells by the oncolytic parvovirus H-1 combined with chemotherapeutic or targeted agents

2010 ◽  
Vol 48 (08) ◽  
Author(s):  
M Moehler ◽  
M Sieben ◽  
S Roth ◽  
B Leuchs ◽  
C Dinsart ◽  
...  
Keyword(s):  
Immune Cells ◽  
Targeted Agents ◽  
Human Immune

THE PROGNOSTIC VALUE OF PD-L1 EXPRESSION IN TUMOR AND IMMUNE CELLS IN SQUAMOUS CELL CARCINOMA OF THE ORAL MUCOSA

2017 ◽  
Vol 63 (5) ◽  
pp. 759-765
Author(s):  
Svetlana Kutukova ◽  
Natalya Belyak ◽  
Grigoriy Raskin ◽  
Marina Mukhina ◽  
Georgiy Manikhas ◽  
...  
Keyword(s):  
Oral Mucosa ◽  
Malignant Tumor ◽  
Immune Cells ◽  
Prognostic Value ◽  
Hard Palate ◽  
Malignant Tumors ◽  
Small Cell ◽  
Alveolar Process ◽  
Small Cell Lung ◽  
Lower Jaw

The most frequent of malignant tumor cites of the oral mucosa are tongue - 55 %, mucosa of the cheek - 12 %, the fundus of the oral cavity - 10 %, the alveolar process of the upper jaw and the hard palate - 9 %, the alveolar process of the lower jaw - 6 %, the soft palate - 2 %. Malignant tumor cells carry PD-L1 ligands on their surface and its expression level is often correlated with an unfavorable prognosis in particular for such tumors as melanoma, kidney cancer and non-small cell lung cancer. It is relevant to evaluate the correlation between overexpression of PD-L1 and overall survival in patients with malignant tumors of the oral mucosa.

RNA-Seq Signatures Normalized by mRNA Abundance Allow Absolute Deconvolution of Human Immune Cells

2018 ◽  
Author(s):  
Gianni Monaco ◽  
Bernett Lee ◽  
Weili Xu ◽  
Seri Mustafah ◽  
You Yi Hwang ◽  
...  
Keyword(s):  
Immune Cells ◽  
Mrna Abundance ◽  
Rna Seq ◽  
Human Immune

scholarly journals 601 Development of improved small molecule STING agonists suitable for systemic administration

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A636-A636
Author(s):  
Maciej Rogacki ◽  
Stefan Chmielewski ◽  
Magdalena Zawadzka ◽  
Jolanta Mazurek ◽  
Katarzyna Wnuk-Lipińska ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Small Molecule ◽  
Immune Cells ◽  
Systemic Administration ◽  
Cytokine Release ◽  
Major Player ◽  
Human Immune ◽  
New Generation ◽  
Dose Dependent ◽  
Complete Tumor

BackgroundStimulator of Interferon Genes (STING) is a major player in the activation of robust innate immune response leading to initiation and enhancement of tumor-specific adaptive immunity. Several clinical and pre-clinical programs have shown that activation of the STING pathway triggers immune-mediated antitumor response. Although vast majority of programs focus on development of analogues of the endogenous STING ligands, their chemical nature and stability often limit their use to local administration. Herein, we present recent results from the development of our selective non-nucleotide, non-macrocyclic, small molecule direct STING agonists, suitable for systemic administration, characterized by improved activity in human immune cells.MethodsBinding to recombinant STING protein was examined using FTS, MST, FP and crystallography studies. Phenotypic screen was performed in THP-1 Dual reporter cells. Mouse bone marrow-derived dendritic cells (BMDC) were obtained from C57BL/6 mice and differentiated with mIL-4 and mGM-CSF. STING agonists were administered into BALB/c mice and cytokine release was measured in plasma. Additionally, mice were inoculated with CT26 murine colon carcinoma or EMT6 murine breast carcinoma cells and the compound was administered, followed by the regular tumor growth and body weight monitoring.ResultsRyvu’s small-molecule agonists demonstrate strong binding affinity to recombinant STING proteins across all tested species. The compounds bind to all human STING protein variants and trigger pro-inflammatory cytokine release from human immune cells regardless of the STING haplotype. Moreover, new generation of developed agonists show significantly improved binding to human protein as well as in vitro activity on human cells. Systemic, intravenous in vivo administration leads to a dose-dependent upregulation of STING-dependent pro-inflammatory cytokines, which results in a dose-dependent antitumor efficacy observed in CT26 and EMT6 mouse cancer models, leading to complete tumor remissions in all treated animals. Furthermore, observed efficacy is accompanied by development of a lasting immunological response demonstrated by lack of tumor engraftment or a delayed tumor growth in cured animals challenged with repeated inoculation of cancer cells.ConclusionsNew generation Ryvu’s STING agonists are strong and selective activators of STING-dependent signaling in both mouse and human immune cells promoting anti-tumor immunity. Treatment with Ryvu’s small-molecule STING agonists leads to engagement of the immune system which results in a complete tumor remission and development of immunological memory of the cancer antigens. The compounds show good selectivity and ADME properties enabling development for systemic administration. In addition developed compounds maintain small functional handles amenable to linker attachment making the series suitable for versatile development as single agents, for combinations with immunotherapies or as targeted agents.

scholarly journals Hyperthermia by near infrared radiation induced immune cells activation and infiltration in breast tumor

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wan Fatin Amira Wan Mohd Zawawi ◽  
M. H. Hibma ◽  
M. I. Salim ◽  
K. Jemon
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Side Effects ◽  
Immune Cells ◽  
Infrared Radiation ◽  
Near Infrared ◽  
Tumor Regression ◽  
Immunohistochemical Analysis ◽  
Therapeutic Effects ◽  
Near Infrared Radiation

AbstractBreast cancer is the most common cancer that causes death in women. Conventional therapies, including surgery and chemotherapy, have different therapeutic effects and are commonly associated with risks and side effects. Near infrared radiation is a technique with few side effects that is used for local hyperthermia, typically as an adjuvant to other cancer therapies. The understanding of the use of near NIR as a monotherapy, and its effects on the immune cells activation and infiltration, are limited. In this study, we investigate the effects of HT treatment using NIR on tumor regression and on the immune cells and molecules in breast tumors. Results from this study demonstrated that local HT by NIR at 43 °C reduced tumor progression and significantly increased the median survival of tumor-bearing mice. Immunohistochemical analysis revealed a significant reduction in cells proliferation in treated tumor, which was accompanied by an abundance of heat shock protein 70 (Hsp70). Increased numbers of activated dendritic cells were observed in the draining lymph nodes of the mice, along with infiltration of T cells, NK cells and B cells into the tumor. In contrast, tumor-infiltrated regulatory T cells were largely diminished from the tumor. In addition, higher IFN-γ and IL-2 secretion was observed in tumor of treated mice. Overall, results from this present study extends the understanding of using local HT by NIR to stimulate a favourable immune response against breast cancer.

scholarly journals The Role of the Bone Marrow Microenvironment in the Response to Infection

2020 ◽  
Vol 11 ◽  
Author(s):  
Courtney B. Johnson ◽  
Jizhou Zhang ◽  
Daniel Lucas
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Immune Cells ◽  
Critical Role ◽  
Primary Source ◽  
Bone Marrow Microenvironment ◽  
Future Research ◽  
Multipotent Stem Cells ◽  
Hematopoietic Stem

Hematopoiesis in the bone marrow (BM) is the primary source of immune cells. Hematopoiesis is regulated by a diverse cellular microenvironment that supports stepwise differentiation of multipotent stem cells and progenitors into mature blood cells. Blood cell production is not static and the bone marrow has evolved to sense and respond to infection by rapidly generating immune cells that are quickly released into the circulation to replenish those that are consumed in the periphery. Unfortunately, infection also has deleterious effects injuring hematopoietic stem cells (HSC), inefficient hematopoiesis, and remodeling and destruction of the microenvironment. Despite its central role in immunity, the role of the microenvironment in the response to infection has not been systematically investigated. Here we summarize the key experimental evidence demonstrating a critical role of the bone marrow microenvironment in orchestrating the bone marrow response to infection and discuss areas of future research.

The Impact of Age and Gender on Hematopoietic Stem Cells and Immune Contexture of the Bone Marrow Microenvironment

2020 ◽  
pp. 1-6
Author(s):  
Rebar N. Mohammed
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Immune Cells ◽  
Absolute Number ◽  
Cell Number ◽  
Hematopoietic Stem ◽  
The Absolute ◽  
And Gender ◽  
The Impact

Hematopoietic stem cells (HSCs) are a rare population of cells that reside mainly in the bone marrow and are capable of generating and fulfilling the entire hematopoietic system upon differentiation. Thirty-six healthy donors, attending the HSCT center to donate their bone marrow, were categorized according to their age into child (0–12 years), adolescence (13–18 years), and adult (19–59 years) groups, and gender into male and female groups. Then, the absolute number of HSCs and mature immune cells in their harvested bone marrow was investigated. Here, we report that the absolute cell number can vary considerably based on the age of the healthy donor, and the number of both HSCs and immune cells declines with advancing age. The gender of the donor (male or female) did not have any impact on the number of the HSCs and immune cells in the bone marrow. In conclusion, since the number of HSCs plays a pivotal role in the clinical outcome of allogeneic HSC transplantations, identifying a younger donor regardless the gender is critical.

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