• Biomedical Science Letters
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• v.27 no.3
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• pp.121-133
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• 2021

Antibody-drug conjugates (ADCs) are drawing much interest due to its great potential to be one of the important options in cancer treatments. ADCs are acting like a magic bullet which delivers cytotoxic drugs specifically to cancerous cells throughout the body, thus attacks these cells, while not harming healthy cells. ADCs are complex molecules that are composed of an antibody having targeting capability and linked-payload or cytotoxic drug killing cancerous cells. The key factors of the success in the development of ADC are selection of appropriate antibody, cytotoxic payload and linker for conjugation. Recently there was considerable progress in ADCs development, and a large number of ADCs gained US FDA approval. About 80 new ADCs are under active clinical studies. In this review we present a brief introduction of the US-FDA approved ADCs and global situation in the clinical studies of ADC pipelines. We address an overview on each component of an ADC design such as target antigens, payloads, linkers, conjugation methods, drug antibody ratio. In addition, we discuss on the trend of ADC market where global big pharmas and domestic biopharmaceutical companies are competing to develop safer and more effective ADCs.

• Biomolecules & Therapeutics
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• v.21 no.6
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• pp.481-486
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• 2013

Macrophages play a role in innate immune responses to various foreign antigens. Many products from primary tumors influence the activation and transmigration of macrophages. Here, we investigated a migration of macrophages stimulated with cancer cell culture-conditioned medium (CM). Macrophage activation by treatment with CM of B16F10 cells were judged by the increase in protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). The location where macrophages were at 4 h-incubation with control medium or CM was different from where they were at 5 h-incubation in culture dish. Percentage of superimposed macrophages at every 1 h interval was gradually increased by CM treatment as compared to control. Total coverage of migrated track expressed in coordinates was smaller and total distance of migration was shorter in CM-treated macrophages than that in control. Rac1 activity in CM-treated macrophages was also decreased as compared to that in control. When macrophages were treated with CM in the presence of dexamethasone (Dex), an increase in COX2 protein levels, and a decrease in Rac1 activity and total coverage of migration were reversed. In the meanwhile, biphasic changes were detected by Dex treatment in section distance of migration at each time interval, which was more decreased at early time and then increased at later time. Taken together, data demonstrate that macrophage motility could be reduced in accordance with activation in response to cancer cell products. It suggests that macrophage motility could be a novel marker to monitor cancer-associated inflammatory diseases and the efficacy of anti-inflammatory agents.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5183-5188
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• 2012

Colorectal cancer remains one of the most widespread malignancies in the world. However, there is a lack of comprehensive studies considering colorectal cancer risk factors among Russian populations, particularly in Siberia. The aim of this investigation was to determine the impact of various lifestyle, dietary, family, and socioeconomical factors on colorectal cancer risk in South-East Siberia. We recruited 185 Russian colorectal cancer cases and 210 gender-, age-, and ethnicity-matched asymptomatic controls with no history of any malignant tumor, using a specially designed questionnaire to obtain relevant information. After the statistical analysis, we defined several significant factors affecting colorectal cancer risk. Among these were smoking (OR=2.13, 95%CI=1.4-3.24, P=0.0004), being overweight (BMI between 25-30, OR=2.45, 95%CI=1.49-4.03, P=0.0004), alcohol drinking (OR=8.73, 95%CI=5.49-13.87, P<0.0001), beer drinking (OR=9.24, 95%CI=5.14-16.61, P<0.0001), consumption of hard liquor (OR=9.37, 95%CI=5.92-14.82, P<0.0001), excessive red meat consumption (P<0.0001), excessive intake of red meat products (P<0.0001), excessive intake of dairy products (P<0.0001), excessive sour cream and cheese consumption (P<0.0001 and 0.0002, respectively), spicy food consumption (OR=2.87, 95%CI=1.9-4.33, P<0.0001), family history of gastrointestinal malignant tumors (OR=3.99, 95%CI=2.09-7.59, P<0.0001), and income exceeding twice the subsistence minimum (OR=5.34, 95%CI=3.35-8.53, P<0.0001). Certain factors, such as high concentration of salt in the food and precancerous colonic lesions, demonstrated borderline significance (OR=3.45, 95%CI=1.68-7.1, P=0.0008, and OR=5.25, 95%CI=1.94-14.22, P=0.001, respectively). Some factors were established as protective, like consumption of rye bread and both rye and wheat bread (OR=0.32, 95%CI=0.21-0.5, P<0,0001, and OR=0.07, 95%CI=0.02-0.21, P<0.0001, respectively), and also low concentration of salt in the food, although this was of borderline significance (OR=0.43, 95%CI=0.26-0.69, P=0.0006). ABO and Rhesus blood antigens were not associated with increased colorectal cancer risk. These results should be definitely applied for elaboration of programs of colorectal cancer prevention in Russia, particularly in Siberia.

• Molecules and Cells
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• v.44 no.5
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• pp.310-317
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• 2021

Cluster of differentiation 1 (CD1) is a family of cell-surface glycoproteins that present lipid antigens to T cells. Humans have five CD1 isoforms. CD1a is distinguished by the small volume of its antigen-binding groove and its stunted A' pocket, its high and exclusive expression on Langerhans cells, and its localization in the early endosomal and recycling intracellular trafficking compartments. Its ligands originate from self or foreign sources. There are three modes by which the T-cell receptors of CD1a-restricted T cells interact with the CD1a:lipid complex: they bind to both the CD1a surface and the antigen or to only CD1a itself, which activates the T cell, or they are unable to bind because of bulky motifs protruding from the antigen-binding groove, which might inhibit autoreactive T-cell activation. Recently, several studies have shown that by producing T_H2 or T_H17 cytokines, CD1a-restricted T cells contribute to inflammatory skin disorders, including atopic dermatitis, psoriasis, allergic contact dermatitis, and wasp/bee venom allergy. They may also participate in other diseases, including pulmonary disorders and cancer, because CD1a-expressing dendritic cells are also located in non-skin tissues. In this mini-review, we discuss the current knowledge regarding the biology of CD1a-reactive T cells and their potential roles in disease.

• Proceedings of the KOSOMBE Conference
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• v.1991 no.05
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• pp.82-85
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• 1991

Cell kinetics and the chemical mass action principle formulate the basis of immune system dynamics which may be synthesized mathematically as cascades of bilinear systems which are connected by nonlinear nondynamical terms. In this manner, a model for cell-mediated immune response (CMI) to tumor antigens and debris is developed. We also consider parametric control variables relevant to the latest experimental data, i.e., sigmoidal dose-response relationship and Michaelis-Menten dynamics. The preliminary results show that the parametric control variable is important in the destruction of tumors. As well as that, the exacerbation theory is a good method for tumor treatment. Finally, tumor control as an application of immunotherapy is analyzed from the basis established above.

• 한국약용작물학회:학술대회논문집
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• 2008.11a
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• pp.344-345
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• 2008

• IMMUNE NETWORK
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• v.12 no.6
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• pp.230-239
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• 2012

Activation-induced cytidine deaminase (AID) is an enzyme that is predominantly expressed in germinal center B cells and plays a pivotal role in immunoglobulin class switch recombination and somatic hypermutation for antibody (Ab) maturation. These two genetic processes endow Abs with protective functions against a multitude of antigens (pathogens) during humoral immune responses. In B cells, AID expression is regulated at the level of either transcriptional activation on AID gene loci or post-transcriptional suppression of AID mRNA. Furthermore, AID stabilization and targeting are determined by post-translational modifications and interactions with other cellular/nuclear factors. On the other hand, aberrant expression of AID causes B cell leukemias and lymphomas, including Burkitt's lymphoma caused by c-myc/IgH translocation. AID is also ectopically expressed in T cells and non-immune cells, and triggers point mutations in relevant DNA loci, resulting in tumorigenesis. Here, I review the recent literatures on the function of AID, regulation of AID expression, stability and targeting in B cells, and AID-related tumor formation.

• BMB Reports
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• v.31 no.1
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• pp.95-100
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• 1998

Two innovative methods to prepare target-sensitive immunoliposomes containing doxorubicin by coupling monoclonal antibodies (mAb DH2, SH1) specific to cancer cell surface antigens ($G_{M3}$, $Le^X$) have been developed and are described here. Firstly, liposomes containing N-glutaryl phosphatidylethanolamine (NGPE) were prepared, followed by the encapsulation of doxorubicin, DH2 or SH1 antibodies were conjugated to NGPE in the liposomes (direct coupling). Secondly, liposomes were prepared with NGPE/mAb conjugates by the detergent dialysis method (conjugate insertion), and then doxorubicin was encapsulated by proton gradient. The immunoliposomes prepared by both methods were able to specifically bind to the surface of the tumor cells - B16BL6 mouse melanoma cells. The efficiencies of doxorubicin-entrapping into liposomes prepared by direct coupling and conjugate insertion was about 98% and 25%, respectively. These types of liposomal formulation are sensitive to target cells, which can be useful for various clinical applications.

• BMB Reports
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• v.50 no.10
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• pp.496-503
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• 2017

The human body loses several billions of cells daily. When cells die in vivo, the corpse of each dead cell is immediately cleared. Specifically, dead cells are efficiently recognized and cleared by multiple types of neighboring phagocytes. Early research on cell death focused more on molecular mechanisms of cell death regulation while the cellular corpses were merely considered cellular debris. However, it has come to light that various biological stimuli following cell death are important for immune regulation. Clearance of normal dead cells occurs silently in immune tolerance. Exogenous or mutated antigens of malignant or infected cells can initiate adaptive immunity, thereby inducing immunogenicity by adjuvant signals. Several pathogens and cancer cells have strategies to limit the adjuvant signals and escape immune surveillance. In this review, we present an overview of the mechanisms of dead cell clearance and its immune regulations.

• IMMUNE NETWORK
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• v.22 no.1
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• pp.6.1-6.19
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• 2022

Chimeric antigen receptor (CAR) T cells, which express a synthetic receptor engineered to target specific antigens, have demonstrated remarkable potential to treat haematological malignancies. However, their transition beyond haematological malignancy has so far been unsatisfactory. Here, we discuss recent challenges and improvements for CAR T cell therapy against solid tumors: Antigen heterogeneity which provides an effective escape mechanism against conventional mono-antigen-specific CAR T cells; and the immunosuppressive tumor microenvironment which provides physical and molecular barriers that respectively prevent T cell infiltration and drive T cell dysfunction and hypoproliferation. Further, we discuss the application of CAR T cells in infectious disease and autoimmunity.