• YAKHAK HOEJI
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• v.55 no.3
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• pp.267-272
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• 2011

Human NK cells, identified 30 years ago based on their ability to spontaneously kill tumor cells, constitute a subset of lymphocytes, which play an important role in the first line of immune defense and the effective function of these cells are enhanced by cytokines. Lung carcinoma has been one of the most commonly diagonosed cancer as well as the leading cause of cancer death in male. Here we provide the evidence that human natural killer cells has inhibitory effects on tumor growth of human lung cancer cell NCI-H460 (non-small cell lung cancer). Enriched NK cell population was obtained by 2 weeks cultivation in interleukin-2(IL-2)-containing medium. The resulting population comprised 26% CD3$^+$ cells, 9% CD3$^+$CD4$^+$ cells, 16% CD3$^+$CD8$^+$ cells, 76% CD56$^+$ cells, 6% CD3$^+$CD56$^+$ cells and 70% CD3$^-$CD56$^+$ cells. Activated NK cells at doese of 2.5, 5, and 10 million cells per mouse inhibited 2%, 12% and 45% of NCI-H460-induced tumor growth in nude mouse xenograft assays, repectively. This result suggests that NK cell-based immunotherapy may be used as an adoptive immunotherapy for lung cancer patients.

• KSBB Journal
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• v.19 no.6 s.89
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• pp.415-420
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• 2004

All around the world, the rate of attack of cancer diseases has been going up and the number of cancer patients has been increasing every year. Cancer can be divided into malignant tumor and benign tumor according to its growth appearance. Many studies and experiments have been conducted and the various treatment are being created to find the way to care malignant. Dendritic cells (DCs), which is an agent of cancer treatments by using an immune reaction in our body, plays an important role to present by a tumor antigen to cytotoxic T-cell and help them to attack the tumor cell directly. However there are some defects of this therapy. Soluble human leukocyte antigen-immunoglobulin fusion protein (HLA-Ig) based artificial antigen presenting cell (aAPC) as the antigen presenting cell (APC) which is complement and overcome some of the limitations of dendritic cell-based vaccines and ex vivo expansion of human T cells is new method for cancer therapy. In this article, we are reviewing the role of DCs and the treatment with it, and searching for the possibility of the new development of immunotherapy for cancer.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.4
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• pp.243-247
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• 2012

Recent studies suggest that immunization with autologous dendritic cells (DCs) results in protective immunity and rejection of established tumors in various human malignancies. The purpose of this study is to determine whether DCs are generated from peripheral blood mononuclear cells (PBMNs) by using cytokines such as F1t-3 ligand (FL), granulocyte macrophage-colony stimulating factor (GM-CSF), IL-4, and TNF-${\alpha}$, and whether cytotoxic T cells activated against the thyroid cancer tissues by the DCs. Peripheral blood was obtained from 2 patients with thyroid cancer. DCs were established from PBMNs by culturing in the presence of FL, GM-CSF, IL-4, and TNF-${\alpha}$ for 14 days. At day 14, the differentiated DCs was analyzed morphologically. The immunophenotypic features of DCs such as CDla, CD83, and CD86 were analyzed by immunofluorelescence microscopy. At day 18, DCs and T cells were incubated with thyroid cancer tissues or normal thyroid tissues for additional 4 days, respectively. DCs generated from the PBMNs showed the typical morphology of DCs. Activated cytotoxic T lymphocytes (CTLs) were observed also. DCs and the CTLs were attached to the cancer tissues on scanning electron microscope. The DCs activated the CTLs, which able to specifically attack the thyroid cancer. This study provides morphologic evidence that the coculture of T cells/cancer tissues activated the T cells and differentiated CTLs. The CTLs tightly adhered to cancer tissues and lysed cancer tissues vigorously. Therefore DCs could be used as potential vaccines in the immunotherapy.

• IMMUNE NETWORK
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• v.20 no.1
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• pp.2.1-2.19
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• 2020

Acute viral infection or vaccination generates highly functional memory CD8 T cells following the Ag resolution. In contrast, persistent antigenic stimulation in chronic viral infection and cancer leads to a state of T-cell dysfunction termed T-cell exhaustion. We and other have recently identified a novel subset of exhausted CD8 T cells that act as stem cells for maintaining virus-specific CD8 T cells in a mouse model of chronic lymphocytic choriomeningitis virus infection. This stem cell-like CD8 T-cell subset has been also observed in both mouse and human tumor models. Most importantly, in both chronic viral infection and tumor models, the proliferative burst of Ag-specific CD8 T cells driven by PD-1-directed immunotherapy comes exclusively from this stem cell-like CD8 T-cell subset. Therefore, a better understanding of the mechanisms how CD8 T-cell subsets are regulated during chronic viral infection and cancer is required to improve the current immunotherapies that restore the function of exhausted CD8 T cells. In this review, we discuss the differentiation of virus-specific CD8 T cells during chronic viral infection, the characteristics and function of CD8 T-cell subsets, and the therapeutic intervention of PD-1-directed immunotherapy in cancer.

• Biomolecules & Therapeutics
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• v.21 no.1
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• pp.10-20
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• 2013

Prostate cancer is one of the most prevalent non-skin related cancers. It is the second leading cause of cancer deaths among males in most Western countries. If prostate cancer is diagnosed in its early stages, there is a higher probability that it will be completely cured. Prostatic acid phosphatase (PAP) is a non-specific phosphomonoesterase synthesized in prostate epithelial cells and its level proportionally increases with prostate cancer progression. PAP was the biochemical diagnostic mainstay for prostate cancer until the introduction of prostate-specific antigen (PSA) which improved the detection of early-stage prostate cancer and largely displaced PAP. Recently, however, there is a renewed interest in PAP because of its usefulness in prognosticating intermediate to high-risk prostate cancers and its success in the immunotherapy of prostate cancer. Although PAP is believed to be a key regulator of prostate cell growth, its exact role in normal prostate as well as detailed molecular mechanism of PAP regulation is still unclear. Here, many different aspects of PAP in prostate cancer are revisited and its emerging roles in other environment are discussed.

• Journal of Digestive Cancer Research
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• v.10 no.1
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• pp.22-30
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• 2022

Immune checkpoint inhibition has been established as a new treatment option for various types of carcinoma, and many clinical trials are being actively conducted as a treatment for advanced or metastatic gastric cancer, either as a monotherapy with an immune checkpoint inhibitor or as a combination therapy with standard chemotherapy. In the CheckMate-649 clinical trial to confirm the efficacy of the combination of nivolumab and chemotherapy (FP) in advanced gastric cancer and gastroesophageal junction cancer, nivolumab group showed improvement in overall survival in programmed death ligand 1-positive cancer patients compared with placebo group. Also, the combination therapy of pembrolizumab, trastuzumab and chemotherapy (FP) in first-line treatment was tested through the KEYNOTE-811 trial. The pembrolizumab group showed 22.7% of improvement in objective response rate compared with placebo group. Accordingly, the combination of nivolumab/pembrolizumab with standard chemotherapy was approved for the first-line treatment. In KEYNOTE-059 trials for patients with progressive disease after at least two lines of chemotherapy, pembrolizumab monotherapy showed improvement in objective response rate and overall survival, and the use of pembrolizumab was approved for the third-line or more treatment. In this article, we review the result of clinical trials related to immune checkpoint inhibitors that have been recently introduced in the treatment of gastric cancer.

• Journal of Digestive Cancer Research
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• v.6 no.1
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• pp.16-24
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• 2018

Gastric cancer is not a single, uniform disease, but rather heterogeneous in nature. It is generally not possible to cure patients with inoperable advanced or metastatic stomach cancer. In the absence of chemotherapy, the median survival time is 3 to 6 months. Therefore, several studies have confirmed the superiority of chemotherapy to the best supportive treatment, in terms of improving the quality of life and prolonging life. Various chemotherapies have been used in the past to treat advanced gastric cancer. Recently, various target therapies and immunotherapy have been introduced. However, compared to other malignancies, the quality of life and life expectancy remain relatively poor in patients with gastric cancer. We expect to overcome these difficulties in the future, with better elucidation of the molecular biology of gastric cancer.

• IMMUNE NETWORK
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• v.22 no.1
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• pp.2.1-2.22
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• 2022

Targeting immune evasion via immune checkpoint pathways has changed the treatment paradigm in cancer. Since CTLA-4 antibody was first approved in 2011 for treatment of metastatic melanoma, eight immune checkpoint inhibitors (ICIs) centered on PD-1 pathway blockade are approved and currently administered to treat 18 different types of cancers. The first part of the review focuses on the history of CTLA-4 and PD-1 discovery and the preclinical experiments that demonstrated the possibility of anti-CTLA-4 and anti-PD-1 as anti-cancer therapeutics. The approval process of clinical trials and clinical utility of ICIs are described, specifically focusing on non-small cell lung cancer (NSCLC), in which immunotherapies are most actively applied. Additionally, this review covers the combination therapy and novel ICIs currently under investigation in NSCLC. Although ICIs are now key pivotal cancer therapy option in clinical settings, they show inconsistent therapeutic efficacy and limited responsiveness. Thus, newly proposed action mechanism to overcome the limitations of ICIs in a near future are also discussed.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7703-7705
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• 2014

Cancer-testis (CT) antigens are a group of tumor-associated antigens with restricted expression in normal tissues except for testis and expression in a wide variety of tumor tissues. This pattern of expression makes them suitable targets for immunotherapy as well as potential biomarkers for early detection of cancer. However, some genes attributed to this family are now known to be expressed in other normal tissues which put their potential applications in immunotherapy and cancer detection under question. Here we analyzed expression of two previously known CT antigens, RHOXF2 and PIWIL2, in AML patients versus normal donors and found no significant difference in the expression of these genes between the two groups. As these two genes showed expression in normal leukocytes, their expression pattern seems to be wider than to be attributed to the CT gene family. Future research should focus on the expression profiles of so called CT antigens to find those with more testis specific expression.

• Journal of Gastric Cancer
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• v.24 no.1
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• pp.29-56
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• 2024

In recent years, remarkable progress has been made in the molecular profiling of gastric cancer. This progress has led to the development of various molecular classifications to uncover subtype-specific dependencies that can be targeted for therapeutic interventions. Human epidermal growth factor receptor 2 (HER2) is a crucial biomarker for advanced gastric cancer. The recent promising results of novel approaches, including combination therapies or newer potent agents such as antibody-drug conjugates, have once again brought attention to anti-HER2 targeted treatments. In HER2-negative diseases, the combination of cytotoxic chemotherapy and programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors has become the established standard of care in first-line settings. In the context of gastric cancer, potential biomarkers such as PD-L1 expression, Epstein-Barr virus, microsatellite instability, and tumor mutational burden are being considered for immunotherapy. Recently, promising results have been reported in studies on anti-Claudin18.2 and fibroblast growth factor receptor 2 treatments. Currently, many ongoing trials are aimed at identifying potential targets using novel approaches. Further investigations will be conducted to enhance the progress of these therapies, addressing challenges such as primary and acquired resistance, tumor heterogeneity, and clonal evolution. We believe that these efforts will improve patient prognoses. Herein, we discuss the current evidence of potential targets for systemic treatment, clinical considerations, and future perspectives.