• YAKHAK HOEJI
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• v.48 no.6
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• pp.335-344
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• 2004

Interleukin-2 (IL-2), a glycoprotein mainly secreted by CD4+ T helper Iymphocytes, has been developed to use recombinant cytokine to augment the immune response against cancer since IL-2 not only stimulates T Iymphocytes but also enhances natural killer (NK) cell activity. In order to evaluate the immunological safety of recombinant mouse IL-2 (rmIL-2) in cancer therapy, renal cell carcinoma was established in the flank by s.c. injection of renca cell line. Tumor-bearing BALB/c mice were treated with I.p. injections with $2{\times}10^5$ Lu rmIL-2. Even though the tumor size was diminished, there were not significant recovery of body and relative lymphoid organ weights including thymic atrophy in rmIL-2 immunotherapy. Distribution ratios of T cell subsets in thymus were analysed using flow cytometry. Without regard to dosage of rmIL-2, the ratio of CD3+CD4-CD8- T cells was increased in accordance with survival of solid tumor but that of CD4+CD8+ T cells was decreased dramatically. Emergence of autoantibodies (ANA, anti-dsDNA, and anti-histone) in blood was measured after rmIL-2 treatment. The results showed that the levels of ANA and anti-dsDNA did not significantly changed, but the level of anti-histone was increased significantly owing to rmIL-2 therapy. These results indicate rmIL-2 immunotherapy is to induce the autoimmune potential, and the anti-histone measurement as a biomarker of autoimmunity is useful in cancer immunotherapy.

• Molecules and Cells
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• v.20 no.2
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• pp.173-182
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• 2005

Heat shock protein gp96 is an endoplasmic reticulum chaperone, belonging to the HSP90 family. The function of gp96 as a molecular chaperone was discovered more than 10 years ago, but its importance has been overshadowed by the brilliance of its role in immune responses. It is now clear that gp96 is instrumental in the initiation of both the innate and adaptive immunity. Recently, the roles of gp96 in protein homeostasis, as well as in cell differentiation and development, are beginning to draw more attention due to rapid development in the structural study of HSP90 and some surprising new discoveries from genetic studies of gp96. In this review, we focus on the aspect of gp96 as an ER molecular chaperone in protein maturation, peptide binding and the regulation of its activity.

• Molecules and Cells
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• v.44 no.8
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• pp.541-548
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• 2021

The discovery of human pluripotent stem cells (PSCs) at the turn of the century opened the door to a new generation of regenerative medicine research. Among PSCs, the donors available for induced pluripotent stem cells (iPSCs) are greatest, providing a potentially universal cell source for all types of cell therapies including cancer immunotherapies using natural killer (NK cells). Unlike primary NK cells, those prepared from iPSCs can be prepared with a homogeneous quality and are easily modified to exert a desired response to tumor cells. There already exist several protocols to genetically modify and differentiate iPSCs into NK cells, and each has its own advantages with regards to immunotherapies. In this short review, we detail the benefits of using iPSCs in NK cell immunotherapies and discuss the challenges that must be overcome before this approach becomes mainstream in the clinic.

• Tuberculosis and Respiratory Diseases
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• v.86 no.1
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• pp.14-22
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• 2023

A significant proportion of patients with non-small cell lung cancer (NSCLC) is diagnosed in the early and resectable stage. Despite the use of platinum-based adjuvant chemotherapy, there was only a marginal increase in overall survival and a 15% decrease in relapse. With the advents of immunotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), the landscape of adjuvant treatment in completely resectable NSCLC is changing. Postoperative radiotherapy can be beneficial to patients who underwent surgical resection in certain clinical settings. In addition, new biomarkers that predict efficacy of EGFR TKI and immunotherapy as adjuvant treatment are also necessary. In this review, recent updates in adjuvant treatment in resectable NSCLC were briefly explained.

• Prospectives of Industrial Chemistry
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• v.22 no.6
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• pp.2-12
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• 2019

최근 암 면역치료는 임상연구에서 긍정적인 결과를 보이고 있으며 암 질환의 표준치료법으로 자리 잡아가고 있다. 암 면역치료는 암의 재발과 전이를 획기적으로 개선시킬 수 있다는 이점이 있다. 하지만 전체 암 환자의 15~20%에서만 치료 효과를 보이고 심각한 부작용을 유발할 수 있다는 임상적 한계가 있다. 이러한 문제점들을 개선하기 위해서 기존에 약물전달 또는 조직공학 분야에서 활용되었던 생체재료를 도입하여 면역치료의 효과를 개선하고 부작용은 줄이려는 시도가 활발하다. 본 기고문에서는 효율적인 암 면역치료를 위한 생체재료(나노입자, 리포좀, 미립구, 및 하이드로젤)에 관한 최신 연구동향을 다루고자 한다. 고기능성 생체재료 개발과 종양 면역학 분야의 깊은 이해는 효과적인 암 면역치료제를 개발하는데 있어서 매우 중요하다.

• Clinical and Experimental Pediatrics
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• v.46 no.5
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• pp.418-422
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• 2003

• IMMUNE NETWORK
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• v.6 no.3
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• pp.154-162
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• 2006

Background: Dendritic cell (DC)-based cancer immunotherapy is studied for several years. However, it is mainly derived from autologous PBMC or leukapheresis from patient, which has limitations about yield and ability of DC production according to individual status. In order to solve these problems, inquiries about allogeneic DCs are performed but there are no preclinical trial answers for effect or toxicity of allogeneic DC to use for clinical trial. In this study, we compared the anti-tumor effect of allogeneic and autologous DCs from mouse bone marrow stem cells in mouse metastatic melanoma model. Methods: B16F10 melanoma cells ($5{\times}10^4$/mouse) were injected intravenously into the C57BL/6 mouse. Therapeutic DCs were differentiated from autologous (C57BL/6: CDC) or allogeneic (B6C3F1: BDC) bone marrow stem cells with GM-CSF, SCF and IL-4 for 13days and pulsed with B16F10 tumor cell lysate (Blys) for 18hrs. DC intra-peritoneal injections began on the 8th day after the tumor cell injection by twice with one week interval. Results: Anti-tumor response was observed by DC treatment without any toxicity especially in allogeneic DC treated mice (tumor burden score: $2.667{\pm}0.184,\;2.500{\pm}0.463,\;2.000{\pm}0.286,\;1.500{\pm}0.286,\;1.667 {\pm}0.297$ for saline, CDC/unpulsed-DC: U-DC, CDC/Blys-DC, BDC/U-DC and BDC/Blys-DC, respectively). IFN-${\gamma}$ secretion was significantly increased in allogeneic DC group stimulated with B16F10 cell lysate ($2,643.3{\pm}5,89.7,\;8,561.5{\pm}2,204.9.\;6,901.2{\pm}141.1pg/1{\times}10^6$ cells for saline, BDC/U-DC and BDC/Blys-DC, respectively) with increased NK cell activity. Conclusion: Conclusively, promising data was obtained that allogeneic DC can be used for DC-based cancer immunotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3843-3847
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• 2015

Background: Cervical cancer is the second most common cause of cancer related death of women. Persistent HPV infection, especially with high-risk types such as HPV16 and HPV18, has been identified to be the primary cause of cervical cancer. E6 and E7 are the major oncoproteins of high-risk HPVs, which are expressed exclusively in HPV infected tissues, and thereby represent ideal therapeutic targets for immunotherapy of cervical cancer. Materials and Methods: In this work, we used recombinant adenovirus expressing coden-optimized HPV16 E6 and E7 fusion protein (Ad-ofE6E7) to prime dendritic cells (DC-ofE6E7), to investigate the ability of primed DC vaccine in eliciting antitumor immunity in vitro and vivo. Results: Our results indicated that DC-ofE6E7 vaccine co-culturing with splenocytes could strongly induce a tumor-specific cytotoxic T lymphocyte (CTL) response and kill the TC-1 cells effectively in vitro. Moreover, DC-ofE6E7 vaccine induced protective immunity against the challenge of TC-1 cancer cells in vivo. Conclusions: The results suggested that the HPV16 ofE6E7 primed DC vaccine has potential application for cervical cancer immunotherapy.

• Journal of Pharmacopuncture
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• v.16 no.1
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• pp.12-20
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• 2013

Objective: Standard cancer therapy prolongs survival, but can be detrimental to the quality of life, compromise the immune system, and leave residual disease that can cause recurrence years or decades in the future. Tumor dormancy therapy is a novel therapeutic approach that may improve these shortcomings, promote quality of life, and prolong survival. The aim of this study was to analyze studies on dormancy therapy, especially studies using traditional Oriental herbal medicine, so as to evaluate the efficacy of dormancy therapy with traditional oriental herbal medicine. Methods: We conducted a systematic literature review using Scientific and Technical Information Integration Services (NDSL), PubMed, and RISS. We searched for clinical reports, papers, and books related to tumor metastasis, recurrence, immunotherapy, tumor dormancy, and traditional oriental herbal medicine with anticancer effects. Seventy-nine (79) experimental and clinical articles in both Korean and English were reviewed. This study was conducted from March 1, 2012 to May 31, 2012. Results: This approach, Tumor dormancy therapy, rather than seeking to remove the tumor, includes combination of low-dose chemotherapy, immunotherapy, immunosurveillance, and other methods to stabilize tumor growth and to enhance the host is immunity against disseminated tumor cells and thus to manage cancer as a chronic disease while maintaining quality of life. In particular, integrative use of Oriental herbal medicine has been shown to induce or maintain tumor dormancy, increase the effectiveness of conventional chemotherapy, improve quality of life, and prolong survival. Conclusion: Tumor dormancy therapy is a promising novel therapeutic approach that may be especially effective with Oriental herbal medicine. Further research is needed to determine its potential mechanisms and therapeutic applications.

• IMMUNE NETWORK
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• v.5 no.3
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• pp.163-171
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• 2005

Background: To perform the successful dendritic cell-based cancer immunotherapy one of the main issues to be solved is the source of antigen for DC pulsing. Limitations occur by using auto-tumor lysate due to the difficulties obtaining enough tumor tissue(s) quantitatively as well as qualitatively. In this study the possibility of allogeneic tumor cell lysate as a DC pulsing antigen has been tested in mouse melanoma pulmonary me tastasis model. Methods: B16F10 melanoma cells $(1{\timeS}10^5/mouse)$ were inoculated intra venously into the C57BL/6 mouse. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 (1,000 U/ml each) for 7 days and pulsed with lysate of either autologous B16F10 (B-DC), allogeneic K1735 (C3H/He origin; K-DC) or CloneM3 (DBA2 origin; C-DC) melanoma cells for 18 hrs. Pulsed-DCs $(1{\times}10^6/mouse)_{[CGP1]}$ were injected i.p. twice with one week interval starting from the day 1 after tumor cell inoculation. Results: Without observable toxicity, allogeneic tumor cell lysate pulsed-DC induced the significantly better anti-tumor response (tumor scale: $2.7{\pm}0.3,\;0.7{\pm}0.3\;and\;0.3{\pm}0.2$ for saline, B-DC and C-DC treated group, respectively). Along with increased tumor specific lymphocyte proliferations, induction of IFN-${\gamma}$ secretion against both auto- and allo-tumor cell lysates was observed from the DC treated mice. (w/B16F10-lysate: $44.97{\pm}10.31,\;1787.94{\pm}131.18,\;1257.15{\pm}48.27$, w/CloneM3 lysate: 0, $1591.13{\pm}1.83,\;1460.47{\pm}86.05pg/ml$ for saline, B-DC and C-DC treated group, respectively) Natural killer cell activity was also increased in the mice treated with tumor cell lysate pulsed-DC ($8.9{\pm}_{[CGP2]}0.1,\;11.6{\pm}0.8\;and\;12.6{\pm}0.7%$ specific NK activity for saline, B-DC and C-DC treated group, respectively). Conclusion: Conclusively, promising data were obtained that allogeneic-tumor cell lysate can be used as a tumor antigen for DC-based cancer immunotherapy.