• Asian Pacific Journal of Cancer Prevention
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• 제16권13호
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• pp.5261-5264
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• 2015

Purpose: To examine the effectiveness of serum free-to-total prostate specific antigen ratio (%fPSA) for the detection of prostate cancer (PCa) in men with different serum total PSA (tPSA) categories. Materials and Methods: From January 2010 to December 2013, a total of 225 patients with lower urinary tract symptoms (LUTS) underwent tPSA and %fPSA measurements. Histological examination with calculation of Gleason score and whole body bone scans were performed in identified cases of PCa. Results: PCa was diagnosed in 44 (19.6%) patients and the remaining 181 patients had benign prostate disease. PCa was detected in 5 (23.8%), 13 (8.7%) and 26 (47.3%) cases with tPSA level ranges ${\leq}4ng/ml$, 4 to 10 ng/ml and >10 ng/ml, respectively. The average Gleason score was $7.2{\pm}0.2$. Some 6 (13.6%) out of 44 PCa patients had bone metastases. The sensitivity was 80% and specificity was 81.3% at the cut-off %fPSA of 15% in PCa patients with a tPSA level below 4 ng/mL. A lower %fPSA was associated with PCa patients with Gleason score ${\geq}7$ than those with Gleason score ${\leq}6$ ($11.7{\pm}0.98$ vs. $16.5{\pm}2.25%$, P=0.029). No obvious relation of %fPSA to the incidence of bone metastasis was apparent in this study. Conclusions: The clinical application of %fPSA could help to discriminate PCa from benign prostate disease in men with a tPSA concentration below 4 ng/mL.

• Journal of Microbiology and Biotechnology
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• 제9권3호
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• pp.346-351
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• 1999

Tumor cells may alter the expression of proteins involved in antigen processing and presentation, allowing them to avoid recognition and elimination by cytotoxic T cells. In order to investigate whether the major histocompatibility complex (MHC) class I-mediated antigen processing machinery is preserved in human lung cancer cell lines, we examined the expression of multiple components of the MHC class I antigen processing pathway, including transporter associated with antigen processing (TAP), $\beta_2$-microglobulin, MHC class I molecules, and chaperones which have not been previously examined in this context. Row cytometry analysis showed that the cell surface expression of MHC class I molecules was downregulated in all of the cell lines. While some cell lines showed no detectable expression of MHC class I molecules, pulse-chase experiments showed that MHC class I molecules were synthesized in the other cell lines but not transported from the endoplasmic reticulum to the cell surface. Low or nondetectable levels of TAP1 and/or TAP2 expression were demonstrated by Western blot analysis in all of the cell lines, representing a variety of lung tissue types. In some cases, this was accompanied by loss of tapasin expression. Our findings suggest that downregulation of antigen processing may be one of the strategies used by tumors to escape immune surveillance. This study provides further information for designing the potential therapeutic applications such as immunotherapy and gene therapy against cancers.

• BMB Reports
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• 제49권6호
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• pp.331-336
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• 2016

In murine collagen-induced arthritis (CIA), self-reactive T cells can recognize peptide antigens derived from type-II collagen (CII). Activation of T cells is an important mediator of autoimmune diseases. Thus, T cells have become a focal point of study to treat autoimmune diseases. In this study, we evaluated the efficacy of recombinant MHC class II molecules in the regulation of antigen-specific T cells by using a self peptide derived from CII (CII260-274; IAGFKGEQGPKGEPG) linked to mouseI-A^q in a murine CIA model. We found that recombinant I-A^q/CII260-274 molecules could be recognized by CII-specific T cells and inhibit the same T cells in vitro. Furthermore, the development of CIA in mice was successfully prevented by in vivo injection of recombinant I-A^q/CII260-274 molecules. Thus, treatment with recombinant soluble MHC class II molecules in complex with an immunodominant self-peptide might offer a potential therapeutic for chronic inflammation in autoimmune disease such as rheumatoid arthritis.

• Journal of Microbiology and Biotechnology
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• 제22권8호
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• pp.1066-1076
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• 2012

Previous observations demonstrated that various immunosuppressive agents and their combination therapies can increase allograft survival rates. However, these treatments may have serious side effects and cannot substantially improve or prolong graft survival in acute graft-versus-host disease (GVHD). To improve the therapeutic potency of divalent immunoadhesins, we have constructed and produced several tetravalent forms of immunoadhesins comprising each of cytotoxic T-lymphocyte-associated antigen-4 (CTLA4), CD2, and lymphocyte activation gene-3 (LAG3). Flow cytometric and T cell proliferation analyses displayed that tetravalent immunoadhesins have a higher binding affinity and more potent efficacy than divalent immunoadhesins. Although all tetravalent immunoadhesins possess better efficacies, tetravalent forms of CTLA4-Ig and LAG3-Ig revealed higher inhibitory effects on T cell proliferation than tetravalent forms of TNFR2-Ig and CD2-Ig. In vitro mixed lymphocytes reaction (MLR) showed that combined treatment with tetravalent CTLA4-Ig and tetravalent LAG3-Ig was highly effective for inhibiting T cell proliferation in both human and murine allogeneic stimulation. In addition, both single tetravalent-form and combination treatments can prevent the lethality of murine acute GVHD. The results of this study demonstrated that co-blockade of the major histocompatibility complex class (MHC)II:T cell receptor (TCR) and CD28:B7 pathways by using tetravalent human LAG3-Ig and CTLA4-Ig synergistically prevented murine acute GVHD.

• 한국가시화정보학회지
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• 제13권1호
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• pp.35-42
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• 2015

CD4+ T-cell count determines the effectiveness for antiretroviral therapy (ART) in patients with human immunodeficiency virus (HIV). Although ART slows the progression of HIV to AIDS, rapid counting of CD4+ T lymphocytes with a drop of patient's blood sample is urgently needed to ensure timely ART treatment in rural areas. Recently point-of-care CD4 testing devices have been developed by using non-flow based imaging cytometer incorporated with a sample cartridge where CD4+ T cells are reacted with fluorescently tagged specific antibodies. Here we conducted an experimental study using a conventional fluorescence microscope-based imaging system to quantitate the interaction of CD4 antibodies with CD4+ T cells at different reaction conditions. We demonstrated that a fast and affordable point-of-care CD4 test is feasible with a far less amount of antibodies and a shorter incubation time compared with a conventional sample preparation protocol for flow cytometry. We also proposed a general method to evaluate and compare the detection limit across different CD4 counting platforms by using fluorescently labelled microbeads for intensity calibration.

• IMMUNE NETWORK
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• 제22권1호
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• pp.4.1-4.22
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• 2022

In the era of immunotherapeutic control of cancers, many advances in biotechnology, especially in Ab engineering, have provided multiple new candidates as therapeutic immuno-oncology modalities. Bispecific Abs (BsAbs) that recognize 2 different antigens in one molecule are promising drug candidates and have inspired an upsurge in research in both academia and the pharmaceutical industry. Among several BsAbs, T cell engaging BsAb (TCEB), a new class of therapeutic agents designed to simultaneously bind to T cells and tumor cells via tumor cell specific antigens in immunotherapy, is the most promising BsAb. Herein, we are providing an overview of the current status of the development of TCEBs. The diverse formats and characteristics of TCEBs, in addition to the functional mechanisms of BsAbs are discussed. Several aspects of a new TCEB-Blinatumomab-are reviewed, including the current clinical data, challenges of patient treatment, drawbacks regarding toxicities, and resistance of TCEB therapy. Development of the next generation of TCEBs is also discussed in addition to the comparison of TCEB with current chimeric antigen receptor-T therapy.

• IMMUNE NETWORK
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• 제1권1호
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• pp.26-31
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• 2001

Background : Follicular dendritic cells (FDCs) play key roles during T cell-dependent humoral immune responses by allowing antigen-specific B cells to survive, proliferate, and differentiate within the FDC networks of secondary follicles, i.e., germinal centers (GC). Methods: A novel monoclonal antibody, 3C8, was generated by immunizing with an FDC line HK, in order to understand the molecular signals involved in the FDC-B cell interactions in the microenvironment of the GC. Results: The 3C8 antibody did not bind to mononuclear cells, including T cells, B cells, and monocytes. Murine L929 and human skin fibroblasts exhibited no or little reactivity to 3C8. However, 3C8 specifically recognized HK cells by flowcytometry. Furthermore, the antigen recognized by 3C8 was restricted to the GC of the human tonsil. Dendritic networks of the GC were intensely stained by 3C8, but cells outside the GC were not. Conclusion: Our results suggest that the antigen 3C8 may play some unique role on FDCs during the GC reactions.

• 대한이식학회지
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• 제28권3호
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• pp.121-134
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• 2014

Current immunosuppressants have nonspecific immuosuppressive effects, and are not helpful for tolerance induction. Consequently, transplant patients cannot discontinue using them, and their nonspecific immunosuppressive effects result in many side effects, including infection and malignancy. However, most of cellular immunotherapy can have donor antigen-specific immunsuppressive effects. Therefore, cell therapy could be an alternative or adjunctive to nonspecific immunosuppressants. Polyclonal or antigen-specific Foxp3+ regulatory T cells have been actively tried for prevention of acute rejection, treatment of chronic rejection, or tolerance induction in clinical trials. Regulatory macrophages are also under clinical trials for kidney transplant patients. IL-10-secreting type 1 regulatory T cells and donor- or recipient-derived tolerogenic dendritic cells will also be used for immunoregulation in clinical trials of kidney transplantation. These cells have antigen-specific immunoregulatory effects. Mesenchymal stromal cells (MSCs) have good proliferative capacity and immunosuppressive actions independently of major histocompatibility complex; therefore, even third-party MSCs can be stored and used for many patients. Cell therapy using various immunoregulatory cells is now promising for not only reducing side effects of nonspecific immunosuppressants but also induction of immune tolerance, and is expected to contribute to better outcomes in transplant patients.

• Journal of Nutrition and Health
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• 제27권10호
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• pp.979-987
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• 1994

We have examined the antigen specificity in orally tolerant mice fed with the casein(CN) diet. In contrast to previous reported results of studies on oral tolerance, these mice responded poorly to ovalbumin(OVA) and ovomucoid(OM), as well as $\alpha$sl-enriched fraction of these cells suppressed anti $\alpha$sl-CN antibody production of naive mice, but could not significantly suppressed antibody response of previously immunized recipient mice. These results indicate that oral tolerance was not medicate through suppressor T cell activities.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.171-172
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• 2002

Immune responses to infectious microbes and foreign antigens are regulated by a series of interactions among T cells, B cells, and antigen-presenting cells (APCs) such as macrophages (M$\square$) and dendritic cells (DCs). The inverse relationship between antibody production and cell-mediated immune responses such as delayed type hypersensitivity (DTH) was experimentally manipulated by varying the dose, route of administration, and form of antigen used to immunize animals. (omitted)