• Biomolecules & Therapeutics
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• v.32 no.4
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• pp.424-431
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• 2024

Among the therapeutic strategies in cancer immunotherapy-such as immune-modulating antibodies, cancer vaccines, or adoptive T cell transfer-T cells have been an attractive target due to their cytotoxicity toward tumor cells and the tumor antigen-specific binding of their receptors. Leveraging the unique properties of T cells, chimeric antigen receptor-T cells and T cell receptor (TCR)-T cells were developed through genetic modification of their receptors, enhancing the specificity and effectiveness of T cell therapy. Adoptive cell transfer of chimeric antigen receptor-T cells has been successful for the treatment of hematological malignancies. To expand T cell therapy to solid tumors, T cells are modified to express defined TCR targeting tumor associated antigen, which is called TCR-T therapy. This review discusses anti-tumor T cell therapies, with a focus on engineered TCR-T cell therapy. We outline the characteristics of TCR-T cell therapy and its clinical application to non-hematological malignancies.

• 한국생물공학회:학술대회논문집
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• 2005.04a
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• pp.322-322
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• 2005

• Journal of Microbiology and Biotechnology
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• v.19 no.10
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• pp.1169-1175
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• 2009

An antifungal chitinase, ChiCW, produced by Bacillus cereus 28-9 is effective against conidial germination of Botrytis elliptica, the causal agent of lily leaf blight. ChiCW as a modular enzyme consists of a signal peptide, a catalytic domain, a fibronectin type-III-like domain, and a chitin-binding domain. When two C-terminal domains of ChiCW were truncated, $ChiCW{\Delta}FC$ (lacking the chitin-binding domain and fibronectin type III-like domain) lost its antifungal activity. Since $ChiCW{\Delta}C$ (lacking the chitin-binding domain) could not be expressed in Escherichia coli as $ChiCW{\Delta}FC$ did, a different strategy based on protein engineering technology was designed to investigate the involvement of the chitin-binding domain of ChiCW ($ChBD_{ChiCW}$) in antifungal activity in this study. Because ChiA1 of Bacillus circulans WL-12 is a modular enzyme with a higher hydrolytic activity than ChiCW but not inhibitory to conidial germination of Bo. elliptica and the similar domain composition of ChiA1 and ChiCW, the C-terminal truncated derivatives of ChiA1 were generated and used to construct chimeric chitinases with $ChBD_{ChiCW}$. When the chitin-binding domain of ChiA1 was replaced with $ChBD_{ChiCW}$, the chimeric chitinase named ChiAAAW exhibited both high enzyme activity and antifungal activity. The results indicate that $ChBD_{ChiCW}$ may play an important role in the antifungal activity of ChiCW.

• Korean Journal of Plant Tissue Culture
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• v.21 no.6
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• pp.353-356
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• 1994

Chimeric kappa chain and gamma chain cDNA clones (pCKS2 and pCHS2) of a monoclonal antibody specific for pre-S2 surface antigen of human hepatitis-B virus were ligated into Xbal site of plant expression vector pBKS-1. Plasmid DNA containing each of the chimeric gene were then mobilized from E, coli to Agrobacterium tumefaciens strain LBA4404. The chimeric antibody genes were then introduced into tobacco by Ti plasmid-mediated transformation. The putative Transformants were selected on medium containing kamaycin sulfate. Shoots that formed on shoot induction medium were analyzed by Western blot analysis for the expression of kappa-chain or gamma-chain genes. The Western blot analyses clearly showed that the introduced genes were stably expressed in transgenic plants.

• Proceedings of the Korea Society of Poultry Science Conference
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• 2005.11a
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• pp.68-69
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• 2005

To identify germline chimeric chicken using germ cell transplantation method, the testcross, spends much time, labor and cost to perform, is the only way for distinguishing germline chimeric chicken from normal one And to enhance the method, development of breed-specific molecular markers have been needed. We have just identified breed-specific sequence polymorphisms among Barred Plymouth rock, Korean Ogol Chicken and White Leghorn in PMEL17 and MC1R gene the loci of which are identical to dominant white and extended black loci. These sequence polymorphism will be very useful for screening germline chimera.

• BMB Reports
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• v.54 no.1
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• pp.44-58
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• 2021

Natural killer (NK) cells, key antitumor effectors of the innate immune system, are endowed with the unique ability to spontaneously eliminate cells undergoing a neoplastic transformation. Given their broad reactivity against diverse types of cancer and close association with cancer prognosis, NK cells have gained considerable attention as a promising therapeutic target for cancer immunotherapy. NK cell-based therapies have demonstrated favorable clinical efficacies in several hematological malignancies but limited success in solid tumors, thus highlighting the need to develop new therapeutic strategies to restore and optimize anti-tumor activity while preventing tumor immune escape. The current therapeutic modalities yielding encouraging results in clinical trials include the blockade of immune checkpoint receptors to overcome the immune-evasion mechanism used by tumors and the incorporation of tumor-directed chimeric antigen receptors to enhance NK cell anti-tumor specificity and activity. These observations, together with recent advances in the understanding of NK cell activation within the tumor microenvironment, will facilitate the optimal design of NK cell-based therapy against a broad range of cancers and, more desirably, refractory cancers.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.3
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• pp.241-256
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• 2023

Although chimeric antigen receptor T cell (CAR-T) is a promising immunotherapy in hematological malignancies, there remain many obstacles to CART cell therapy for solid tumors. Identifying appropriate tumor-associated antigens (TAAs) is especially critical for success. Using a bioinformatics approach, we identified common potential TAAs for CAR-T cell immunotherapy in solid tumors. We used the GEO database as a training dataset to find differentially expressed genes (DEGs) and verified candidates using the TCGA database, obtaining seven common DEGs (HM13, SDC1, MST1R, HMMR, MIF, CD24, and PDIA4). Then, we used MERAV to analyze the expression of six genes in normal tissues to determine the ideal target genes. Finally, we analyzed tumor microenvironment factors. The results of major microenvironment factor analyses showed that MDSCs, CXCL1, CXCL12, CXCL5, CCL2, CCL5, TGF- β, CTLA-4, and IFN-γ were significantly overexpressed in breast cancer. The expression of MST1R was positively correlated with TGF- β, CTLA-4, and IFN-γ. In lung adenocarcinoma, MDSCs, Tregs, CXCL12, CXCL5, CCL2, PD-L1, CTLA-4, and IFN-γ were significantly overexpressed in tumor tissues. The expression of MST1R was positively correlated with TGF- β, CTLA-4, and IFN-γ. In bladder cancer, CXCL12, CCL2, and CXCL5 were significantly overexpressed in tumor tissues. MST1R expression was positively correlated with TGF- β. Our results demonstrate that MST1R has the potential as a new target antigen for treating breast cancer, lung adenocarcinoma, and bladder cancer and may be used as a progression indicator for bladder cancer.

• Biomedical Science Letters
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• v.10 no.4
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• pp.391-395
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• 2004

The demand for the production of gene-defective mice from embryonic stem (ES) cells is increasing to clarify decisive gene function in vivo. Although blastocyst injection is widely used to generate ES cell-mediated knockout mice, coculture method has been alternatively used because of several advantages, such as low cost and simple procedure. Thus, this experiment was designed to demonstrate the feasibility of the coculture method using J1 ES cells, which are known to be efficient for blastocyst injection. Eight-cell embryos were harvested from 2.5 days post-coitum (dpc), denuded with acid tyrode's solution, and transferred onto trypsinized J1 ES cells. Aggregation was carried out following two typical methods, which are simple coculture method and aggregation in groove prepared by aggregation needle. Successfully aggregated-embryos were developed to blastocysts for 24 h and transferred into uterus of pseudo-pregnant foster mother. Chimeric offspring was judged by coat pigmentation. In this study, we could obtain chimeric mice from all the two aggregation methods, but the chimera production efficiencies in coculture using groove were three times higher at least than those in the other group. In conclusion, these observations suggest that coculture method should be available for production of knockout mice from J1 ES cells. Presently, the germ-line transmission rates of the chimeras produced from the two methods are under investigation.

• Microbiology and Biotechnology Letters
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• v.38 no.2
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• pp.151-157
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• 2010

Barley malt produces two different $\alpha$-amylase isozymes (AMY1 and AMY2), which share up to 80% of amino acid sequence identity with each other. However, their enzymatic properties differ remarkably. In this study, five chimeric enzymes between AMY1 and 2 were constructed by staggered extension process (StEP) technique, and their enzymatic properties were characterized. According to the results, chimeric AMY-D2, D8, and E12 showed the mixed or intermediate types of calcium-dependent activity between AMY1 and 2. Meanwhile, only AMY-E10 chimera could be significantly inhibited by barley $\alpha$-amylase/subtilisin inhibitor (BASI) protein. Chimera AMY-C6 showed the same calcium-dependency as AMY1, while AMY-E10 was closely similar to AMY2. As a result, it can be proposed that some amino acid residues in the region II, III, and IV of barley $\alpha$-amylases can play very important roles in the interaction with BASI, and those in III, V, VI, and VII may partly affect on the calcium-dependent activity.

• Korean Journal of Poultry Science
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• v.49 no.2
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• pp.69-77
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• 2022

Antimicrobial peptides (AMPs) play an important role in innate immunity against pathogenic infections. AMPs exterminate pathogenic bacteria by disrupting cell membranes or inhibiting intracellular molecules. NK-2, first identified in pigs and derived from NK-lysin, has antimicrobial effects against bacteria and parasites. In this study, chimeric peptides (cpNK) of chicken and pig NK-2 and cpNK-derived peptides (cpNK-a1 and cpNK-a2) were synthesized, and their antimicrobial effects against various pathogenic bacteria such as Escherichia coli, Salmonella spp., Listeria monocytogenes, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus (MRSA) were investigated. The structure of chimeric peptides from chicken and pig NK-2, cpNK, include α-helix like NK-2 and peptide net charge was +9 like porcine NK-2. The cpNK peptide showed powerful bactericidal effects against most bacterial species, including MRSA, especially against gram-negative bacteria. Furthermore, cpNK-derived short peptides, cpNK-a1 and a2 also showed bactericidal activity, but the effects were weaker than those of cpNK. Therefore, we conclude that cpNK- and cpNK-derived short peptides have the potential to be used as antibiotic alternatives.