• BMB Reports
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• 제54권1호
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• pp.70-88
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• 2021

Immunotherapy has revolutionized the landscape of cancer treatment and become a standard pillar of the treatment. The two main drivers, immune checkpoint inhibitors and chimeric antigen receptor T cells, contributed to this unprecedented success. However, despite the striking clinical improvements, most patients still suffer from disease progression because of the evolution of primary or acquired resistance. This mini-review summarizes new treatment options including novel targets and interesting combinational approaches to increase our understanding of the mechanisms of the action of and resistance to immunotherapy, to expand our knowledge of advances in biomarker and therapeutics development, and to help to find the most appropriate option or a way of overcoming the resistance for cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• 제16권7호
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• pp.3079-3081
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• 2015

Cancer-testis antigens (CTAs) are a group of tumor associated antigens with a restricted expression pattern in normal gametogenic tissues but expression in a broad range of malignancies. Their expression pattern has made them potential targets for immunotherapy. However, expression of some of these antigens has been demonstrated in normal stem cells as well as cancer stem cells (CSCs). As CSCs have been shown to be sources of metastasis and tumor recurrence, novel therapies are being focused on their eradication. On the other hand, CTA expression in normal stem cells raises the possibility that CTA based immunotherapies cause side effects in normal tissues.

• 한국임상약학회지
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• 제28권1호
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• pp.65-75
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• 2018

Objective: Over the last several years, immunotherapy has become one of the most promising therapeutic options for cancer. This study aims to summarize the updates on cancer immunotherapy focusing on immune checkpoint inhibitors, such as programmed cell death-1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, which have received attention as new anticancer therapeutic agents. Methods: A literature survey was carried out on PubMed to identify high-impact papers on cancer immunotherapy from 2010. The most recent data on clinical efficacy and safety have been included highlighting the response characteristics to recently approved immunotherapeutic agents. Results: In various cancers, immune checkpoints are a means for cancer cells to evade the immune system. Furthermore, CTLA-4 and PD-L1 can be overexpressed, allowing malignant cells to evade T-cells. Numerous clinical trials have been performed to seek appropriate indication of these products in various cancer types. Among them, the most conspicuous types are melanoma, non-small-cell lung cancer, and head and neck cancer. The approval of ipilimumab by Food and Drug Administration (FDA) commenced a new era of cancer immunotherapy. This was followed by the approval of nivolumab and pembrolizumab. Currently, combination therapies are being investigated for various cancer types. Conclusion: In this study, we reviewed recently reported scientific and clinical evidence for currently approved immune checkpoint inhibitors. Although these novel checkpoint inhibitors are ever evolving for cancer therapies, there exist limitations that need to be overcome, indicating the necessity for further studies aiming to improve their efficacy, toxicity, and cost.

• IMMUNE NETWORK
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• 제14권6호
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• pp.265-276
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• 2014

The interactions between B7 molecules and CD28-family receptors are crucial in the regulation of adaptive cellular immunity. In cancer, the aberrant expression of co-inhibitory B7 molecules has been attributed to reduced anti-tumor immunity and cancer immune evasion, prompting the development of cancer therapeutics that can restore T cell function. Murine tumor models have provided significant support for the targeting of multiple immune checkpoints involving CTLA-4, PD-1, ICOS, B7-H3 and B7-H4 during tumor growth, and clinical studies investigating the therapeutic effects of CTLA-4 and PD-1 blockade have shown exceptionally promising results in patients with advanced melanoma and other cancers. The expression pattern of co-inhibitory B7 ligands in the tumor microenvironment has also been largely correlated with poor patient prognosis, and recent evidence suggests that the presence of several B7 molecules may predict the responsiveness of immunotherapies that rely on pre-existing tumor-associated immune responses. While monotherapies blocking T cell co-inhibition have beneficial effects in reducing tumor burden, combinatorial immunotherapy targeting multiple immune checkpoints involved in various stages of the anti-tumor response has led to the most substantial impact on tumor reduction. In this review, we will examine the contributions of B7- and CD28-family members in the context of cancer development, and discuss the implications of current human findings in cancer immunotherapy.

• IMMUNE NETWORK
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• 제22권1호
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• pp.5.1-5.22
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• 2022

The approval of immunotherapies such as checkpoint inhibitors (CPIs), adoptive cell therapies and cancer vaccines has revolutionized the way cancer treatment is approached. While immunotherapies have improved clinical outcome in a variety of tumor types, some cancers have proven harder to combat using single agents, underscoring the need for multi-targeted immunotherapy approaches. Efficacy of CPIs and cancer vaccines requires patients to have a competent immune system with adequate cell numbers while the efficacy of adoptive cellular therapy is limited by the expansion and persistence of cells after infusion. A promising strategy to overcome these challenges is combination treatment with common gamma-chain cytokines. Gamma-chain cytokines play a critical role in the survival, proliferation, differentiation and function of multiple immune cell types, including CD8 T-cells and NK cells, which are at the center of the anti-tumor response. While the short halflife of recombinant cytokines initially limited their application in the clinic, advancements in protein engineering have led to the development of several next-generation drug candidates with dramatically increased half-life and bioactivity. When combining these cytokines with other immunotherapies, strong evidence of synergy has been observed in preclinical and clinical cancer settings. This promising data has led to the initiation of 70 ongoing clinical trials including IL-2, IL-7, IL-15 and IL-21. This review summarizes the recent advancements of common gamma-chain cytokines and their potential as a cancer immunotherapy.

• Journal of Gastric Cancer
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• 제23권1호
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• pp.207-223
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• 2023

Gastric cancer (GC) is the fourth leading cause of cancer-related deaths worldwide. Under the standard of care, patients with advanced GC (AGC) have a median survival time of approximately 12-15 months. With the emergence of immunotherapy as a key therapeutic strategy in medical oncology, relevant changes are expected in the systemic treatment of GC. In the phase III ATTRACTION-2 trial, nivolumab, a monoclonal anti-programmed cell death 1 (PD-1) antibody, as a third- or later-line treatment improved overall survival (OS) compared with placebo in patients with AGC. Furthermore, nivolumab in combination with 5-fluorouracil and platinum as a first-line treatment improved OS in patients with human epidermal growth factor receptor-2 (HER2)-negative AGC in the global phase III CheckMate-649 study. Another anti-PD-1 antibody, pembrolizumab, in combination with trastuzumab and cytotoxic chemotherapy as a first-line treatment, significantly improved the overall response rate in patients with HER2-positive AGC. Therefore, immune checkpoint inhibitors (ICIs) are essential components of the current treatment of GC. Subsequent treatments after ICI combination therapy, such as ICI rechallenge or combination therapy with agents having other modes of action, are being actively investigated to date. On the basis of the success of immunotherapy in the treatment of AGC, various clinical trials are underway to apply this therapeutic strategy in the perioperative and postoperative settings for patients with early GC. This review describes recent progress in immunotherapy and potential immunotherapy biomarkers for GC.

• 대한의생명과학회지
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• 제29권4호
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• pp.371-375
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• 2023

Natural killer (NK) cells are innate immune cells and play important roles as the first immune cells to recognize and kill cancer. In patients with advanced and terminal cancer, NK cells are often inactivated, suggesting that NK cells may play important roles in cancer treatment. In particular, the proportion of NK cells among immune cells infiltrating tumor tissues is often low, which suggests that NK cells do not survive in tumor microenvironment (TME). In order to overcome these hurdles of NK cells in cancer treatment, it is critical to develop strategies that enhance the proliferation and cytolytic activity of NK cells. We applied Vemurafenib to NK cells and measured the degree of NK cell proliferation and functional activation. We obtained unexpected results of increased NK cell numbers and anti-tumor activity after Vemurafenib treatment. Although further investigation is required to uncover the detailed mechanisms, our results suggest that Vemurafenib is a promising candidate to increase the efficacy of cancer immunotherapy using NK cells.

• 대한의생명과학회지
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• 제29권4호
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• pp.382-385
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• 2023

NK (Natural killer) cells are innate immune cells and play important roles as the first immune cells to act when cancer occurs. In many cancer patients, NK cells can be seen to be inactivated, suggesting that NK cells are important in cancer treatment. In order to overcome the disadvantages of NK cells in cancer treatment, it is critical to develop strategies that enhance the proliferation and cytolytic function of NK cells. We applied niclosamide to measure the degree of NK cell activation, and obtained unexpected results of increased NK cell numbers and anti-tumor activity. Although further investigation is required to uncover the detailed mechanisms, our results suggest that Niclosamide is a promising candidate to increase the efficacy of cancer immunotherapy using NK cells.

• BMB Reports
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• 제52권11호
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• pp.647-652
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• 2019

G protein-coupled estrogen receptor (GPER) is known to play an important role in hormone-associated cancers. G-1, a novel synthetic GPER agonist, has been reported to exhibit anti-carcinogenic properties. However, the chemotherapeutic mechanism of GPER is yet unclear. Here, we evaluated GPER expression in human gastric cancer tissues and cells. We found that G-1 treatment attenuates GPER expression in gastric cancer. GPER expression increased G-1-induced antitumor effects in mouse xenograft model. We analyzed the effects of knockdown/overexpression of GPER on G-1-induced cell death in cancer cells. Increased GPER expression in human gastric cancer cells increased G-1-induced cell death via increased levels of cleaved caspase-3, -9, and cleaved poly ADP-ribose polymerase. Interestingly, during G-1-induced cell death, GPER mRNA and protein expression was attenuated and associated with ER stress-induced expression of PERK, ATF-4, GRP-78, and CHOP. Furthermore, PERK-dependent induction of ER stress activation increased G-1-induced cell death, whereas PERK silencing decreased cell death and increased drug sensitivity. Taken together, the data suggest that the induction of ER stress via GPER expression may increase G-1-induced cell death in gastric cancer cells. These results may contribute to a new paradigm shift in gastric cancer therapy.

• Journal of Digestive Cancer Research
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• 제6권2호
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• pp.45-49
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• 2018

Colorectal cancer (CRC) is the third most common cause of cancer-related death in the world. Although the long-term outcome of patients with metastatic CRC is still poor, target therapy including anti EGFR agents and anti VEGF agents and immunotherapy including anti PD-1 antibody and anti CTLA-4 antibody have shown clinical benefits in the treatment of patient with metastatic CRC. In the future, the personalized treatment strategy based on the clinical characteristics and biologic features of patients with metastatic CRC will be necessary. In this review, we summarized the mechanisms and clinical evidences of target therapy and immunotherapy, and the guideline of clinical practice in patients with metastatic CRC.