• 한국동물위생학회지
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• 제25권3호
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• pp.309-314
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• 2002

Recombinant interleukin-2(IL-2) has demonstrated as an antineoplastic agent in mice and human, but the relatively low response rates observed in clinical trials. Therefore, the present study was undertaken in order to evaluate therapeutic activities of IL-2 for the establishment of therapeutic applications. At the onset of the experiment, normal C3H/HeN mice were injected with 5$\times$10$\^$6/ RD-995 tumor cells, murine ultraviolet radiation-induced fibrosarcoma, intraperitoneally. Beginning on day 6, experimental groups were treated with a 5-day course of IL-2(subcutaneous injection of 30,000 IU every 12 hours for 5 days). The result of this experiment revealed that body weight gradually decreased from 20th day in control mice. Subcutaneous IL-2 therapy prevented partially decrease body weight, and prolonged survival of mice compared with control group.

• IMMUNE NETWORK
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• 제20권1호
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• pp.3.1-3.20
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• 2020

Immune checkpoint inhibitors (ICIs), including anti-PD-1 and anti-CTLA-4 therapeutic agents, are now approved by the Food and Drug Administration for treatment of various types of cancer. However, the therapeutic efficacy of ICIs varies among patients and cancer types. Moreover, most patients do not develop durable antitumor responses after ICI therapy due to an ephemeral reversal of T-cell dysfunction. As co-stimulatory receptors play key roles in regulating the effector functions of T cells, activating co-stimulatory pathways may improve checkpoint inhibition efficacy, and lead to durable antitumor responses. Here, we review recent advances in our understating of co-stimulatory receptors in cancers, providing the necessary groundwork for the rational design of cancer immunotherapy.

• 혜화의학회지
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• 제12권2호
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• pp.157-175
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• 2004

The purpose of this study was to investigate the effects of Hangamdan(抗癌丹). The clinical study was carried out 320 cases of patients with cancer treated by Hangamdan(抗癌丹) from May 1st 1998 to September 1st 1999. The results were summarized as follows; 1. The effects of improvement in the symptoms with traditional oriental cancer therapy(47.6%) were higher than combined treatment of western and oriental therapy(37.4%). 2. In the analysis of hematology, maintenance and increasing of WBC(86.2%), Hgb(87.2%), P1atelet(97.6%) RBC(81.1%) were observed. In the analyses of tumor marker, maintenance and decreasing of CEA(76%), CA19-9(88.8%), AFP(69.2%) were observed. 3. In the analysis of safety, maintenance and decreasing of AST(93.1%), ALT(95%), BUN(92.2%), Creatinine(93.6%) were observed. 4. In the analysis of QOL attached by cancer, combined treatment of western and oriental therapy(maintenance and improvement; 91.8%) was higher than traditional oriental cancer therapy(maintenance and improvement; 79.3%) 5. In the analysis of survival in patients with terminal cancer, above 6 months(46.3%), 12 months(19.2%). 6. In the analysis of antitumor effects, combined treatment of western and oriental therapy(maintenance 71.6% improvement 12.8%) was higher than traditional oriental therapy (maintenance 66.7% improvement 9.5%). 7. In the analysis of curative evaluation, combined treatment of western and oriental therapy(maintenance 40.4% improvement 41.8%) was higher than traditional oriental therapy (maintenance 23.8% improvement 46.1%). 8. In the analysis of IL-12 and IFN-$\gamma$ attached by cancer, increasing of IL-12(32.3%), IFN-$\gamma$(41.5%) were observed. From the above results, it is suggested that Hangamdan has significant effects of antitumor and immune activity, also could be usefully applied for cancer patients by combination with western therapy or alone.

• 대한한방종양학회지
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• 제6권1호
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• pp.165-180
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• 2000

Clinical studies were carried out 83 cases of patients with colorectal cancer treated by Hangamdan(抗癌丹) from January 1th 1998 to September 30th 2000. The results were summarized as follows; 1. Distribution of those attached by colorectal cancer, by sex, showed that Male is more then Female, by age, showed that the number of fifties is majority. 2. Distribution of diagnostic stage, in descending order; stage III(53%, top), stage IV(45.8%). 3. The effects of maintenance and improvement in the symptoms with traditional oriental therapy(83.3%) and combined treatment of western and oriental therapy(92.1%) were observed. The effects of the symptoms were as follows: diarrhea(37.3%), abdominal pain (25.3%), general body weakness(22.9%), nausea(20.5%) and etc. in orders. 4. Analysis of hematology attached by colorectal cancer, maintenance and increasing of WBC(89.9%), RBC(74.7%), Hgb(81.1%), Platelet(92.4%) were observed. After taken Hangamdan, the safety of the liver and kidney were as follows; maintenance and decreasing of AST(85.9%), ALT(94.8%), GTP(87.5%), Creatinine(90.9%) were observed. 5. of IL-12 and $IFN-\gammer$ attached by colorectal cancer, increasing of IL-12(53.3%), IFN-{\gammer}(80%)$) were observed. 6. Analysis of QOL attached by colorectal cancer, maintenance and improvement of combined treatment of western and oriental therapy(89.6%), traditional oriental therapy(83.3%) were observed. 7. Analysis of survival in patients with IV stage of colorectal cancer, above 7 months(18.4%), 12 months(65.8%). 8. Analysis of antitumor effects, maintenance of traditional oriental therapy(83.3%) and maintenance and improvement of combined treatment of western and oriental therapy(80.5%) were observed. Analysis of tumor marker attached by colorectal cancer, maintenance and decreasing of CEA(78.8%) were observed. 9. Analysis of curative valuation, maintenance and improvement of traditional oriental therapy(83.3%), combined treatment of western and oriental therapy(72.7%) were observed. From the above results, it is suggested that Hangamdan has significant effects of antitumor and immune activity, also could be usefully applied for colorectal cancer patients by combination with western therapy or alone.

• 혜화의학회지
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• 제10권1호
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• pp.121-131
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• 2001

Clinical studies were carried out 62 cases of patients with lung cancer treated by Hangamdan(抗癌丹) from January 1th 1998 to September 30th 2000. The results were summarized as follows; 1. Distribution of those attached by lung cancer, by sex, showed that Male is more then Female, by age, showed that the number of sixties is majority. 2. Distribution of diagnostic stage, in descending order; stage IV(43.6%,top), stage III(35.5%), stage II(17.7%), stage I(3.2%). 3. The effects of maintenance and improvement in the symptoms with traditional oriental therapy(83.3%) and combined treatment of western and oriental therapy(84.0%) were observed. The effects of the symptoms were as follows; cough(50.0%), anorexia(48.4%), chest discomfort(31.0%), sputum(24.2%), general body weakness(11.3%), hemoptysis(9.7%) and etc. in orders. 4. Analysis of hematology attached by lung cancer, maintenance and increasing of WBC(98.4%), RBC(74.2%), Hgb(71.0%), Platelet(96.7%) were observed. After taken Hangamdan, the safety of the liver and kidney were as follows; maintenance and decreasing of AST(91.5%), ALT(93.2%), ${\gamma}-GTP$(95.0%), BUN(82.7%), Creatinine(93.3%) were observed. 5. Analysis of IL-12 and $IFN-{\gamma}$ attached by lung cancer, increasing of IL-12(31.3%), $IFN-{\gamma}$(72.7%) were observed. 6. Analysis of QOL attached by lung cancer, maintenance and improvement of combined treatment of western and oriental therapy(94.0%), traditional oriental therapy(91.7%) were observed. 7. Analysis of survival in patients with IV stage of lung cancer, above 7 months(22.2%), 12 months(70.4%). 8. Analysis of antitumor effects, maintenance of traditional oriental therapy(50.0%) and maintenance and improvement of combined treatment of western and oriental therapy(80.0%) were observed. 9. Analysis of curative valuation, maintenance and improvement of traditional oriental therapy(50.0%), combined treatment of western and oriental therapy(60.0%) were observed. From the above results, it is suggested that Hangamdan has significant effects of antitumor and immune activity, also could be usefully applied for lung cancer patients by combination with western therapy or alone.

• IMMUNE NETWORK
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• 제9권5호
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• pp.158-168
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• 2009

Tumor therapy using cytokines has been developed for last two decades. Several recombinant cytokines and tumor cell vaccines produced by cytokine gene transfer have been in clinical trials, but several side effects hamper routine clinical applications. Many cytokines are originally expressed as membrane-bound form and then processed to secretory form exerting paracrine effects. Though functional differences of these two types of cytokines are elusive yet, the membrane-bound form of cytokine may exert its effects on restricted target cells as a juxtacrine, which are in physical contacts. With the efforts to improve antitumor activities of cytokines in cancer patients, developing new strategies to alleviate life-threatening side effects became an inevitable goal of tumor immunologists. Among these, tumor cell vaccines expressing cytokines as membrane-bound form on tumor cell surface have been developed by genetic engineering techniques with the hope of selective stimulation of the target cells that are in cell-to-cell contacts. In this review, recent progress of tumor cell vaccines expressing membrane-bound form of cytokines will be discussed.

• Radiation Oncology Journal
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• 제37권4호
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• pp.302-308
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• 2019

The abscopal effect is a term that has been used to describe the phenomenon in which localized radiation therapy treatment of a tumor lesion triggers a spontaneous regression of metastatic lesion(s) at a non-irradiated distant site(s). Radiation therapy induced abscopal effects are believed to be mediated by activation and stimulation of the immune system. However, due to the brain's distinctive immune microenvironment, extracranial abscopal responses following cranial radiation therapy have rarely been reported. In this report, we describe the case of 42-year-old female patient with metastatic melanoma who experienced an abscopal response following her cranial radiation therapy for her brain metastasis. The patient initially presented with a stage III melanoma of the right upper skin of her back. Approximately 5 years after her diagnosis, the patient developed a large metastatic lesion in her upper right pectoral region of her chest wall and axilla. Since the patient's tumor was positive for BRAF and MEK, targeted therapy with dabrafenib and trametinib was initiated. However, the patient experienced central nervous system (CNS) symptoms of headache and disequilibrium and developed brain metastases prior to the start of targeted therapy. The patient received radiation therapy to a dose of 30 Gy delivered in 15 fractions to her brain lesions while the patient was on dabrafenib and trametinib therapy. The patient's CNS metastases improved significantly within weeks of her therapy. The patient's non-irradiated large extracranial chest mass and axilla mass also shrank substantially demonstrating the abscopal effect during her CNS radiation therapy. Following radiation therapy of her residual chest lesions, the patient was disease free clinically and her CNS lesions had regressed. However, when the radiation therapy ended and the patient continued her targeted therapy alone, recurrence outside of her previously treated fields was noted. The disease recurrence could be due to the possibility of developing BRAF resistance clones to the BRAF targeted therapy. The patient died eventually due to wide spread systemic disease recurrence despite targeted therapy.

• Tuberculosis and Respiratory Diseases
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• 제51권2호
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• pp.135-146
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• 2001

배 경 : 암세포는 정상 세포와 다르므로 면역 기전에 의해 제거되어야 함에도 불구하고 암이 발생하는 것은 암세포가 면역 감시 체계를 회피하기 때문이다. 약제감수성 증강 유전자인 herpes simplex thymidine kinase(HSTK) 유전자를 이용하여 암세포를 파괴하여 종양 특이항원이 더 잘 유리되도록 하고 사이토카인 유전자를 이용하여 면역세포를 유도하여 이 장애를 극복할 수 있는지 보고자 이 실험을 하였다. 방 법 : Lewis 폐암 세포주(LLC)에 adenovirus를 이용하여 HSTK를 형질도입하고 이에 의해 ganciclovir에 대한 LLC의 감수성을 증강시키는지를 관찰하고 mixed population assay를 이용하여 bystander 효과를 관찰하였다. Ad-HSTK, Ad-IL-2, Ad-GMCSF의 형질도입이 LLC의 종양 형성 능력에 영향을 미치는지 관찰하였다. 또한 그러한 형질 도입이 기존의 종양에 대한 항암 효과를 가져오는지 관찰하였다. 항암 효과의 기전을 확인하기 위해 쥐의 비장을 관찰하였다. 결 과 : Ad-HSTK의 형질도입은 ganciclovir에 대한 LLC의 감수성을 현저하게 증강시켰다. Ad-HSTK, Ad-IL-2, Ad-GM-CSF를 형질도입한 LLC를 쥐에 주사하고 ganciclovir로 처리하였을 때 종양 형성 능력이 감소하였다. Ad-HSTK, Ad-IL-2, Ad-GM-CSF를 형질도입한 LLC를 종양백신으로 사용하였을때 종양 성장이 어느 정도 저해되는 것을 관찰하였다. 특히 HSTK와 GM-CSF를 복합 형질도입했을 때 더 강력한 항암효과가 일어나는 것을 관찰하였다. 그러나 HSTK와 IL-2을 복합 형질도입했을 때는 각각을 단독으로 형질도입했을 때보다 항암효과가 상승되지 않았다. HSTK와 GM-CSF의 복합 형질도입한 LLC를 종양백신으로 사용하였을 때 비장의 수상세포 침윤이 현저히 증가하였다. 결 론 : HSTK와 GM-CSF의 복합 형질도입으로 만든 종양백신은 수상세포를 활성화시키므로써 항암면역기능을 유의하게 증강시킬 수 있었다.

• BMB Reports
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• 제51권11호
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• pp.572-577
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• 2018

Recent studies showed that the PD-1/PD-L1 checkpoint blockade is a dramatic therapy for melanoma by enhancing antitumor immune activity. Currently, major strategies for the PD-1/PD-L1 blockade have mainly focused on the use of antibodies and compounds. Seeking an alternative approach, others employ endogenous proteins as blocking agents. The extracellular domain of PD-1 (ePD1) includes the binding site with PD-L1. Accordingly, we constructed a PD-1-based recombinantly tailored fusion protein (dFv-ePD1) that consists of bivalent variable fragments (dFv) of an MMP-2/9-targeted antibody and ePD1. The melanoma-binding intensity and antitumor activity were also investigated. We found the intense and selective binding capability of the protein dFv-ePD1 to human melanoma specimens was confirmed by a tissue microarray. In addition, dFv-ePD1 significantly suppressed the migration and invasion of mouse melanoma B16-F1 cells, and displayed cytotoxicity to cancer cells in vitro. Notably, dFv-ePD1 significantly inhibited the growth of mouse melanoma B16-F1 tumor cells in mice and in vivo fluorescence imaging showed that dFv-ePD was gradually accumulated into the B16-F1 tumor. Also the B16-F1 tumor fluorescence intensity at the tumor site was stronger than that of dFv. This study indicates that the recombinant protein dFv-ePD1 has an intensive melanoma-binding capability and exerts potent therapeutic efficacy against melanoma. The novel format of the PD-L1-blocked agent may play an active role in antitumor immunotherapy.

• 한국임상수의학회지
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• 제28권6호
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• pp.549-554
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• 2011

FK506은 말기 간암환자의 간이식 후 널리 사용되는 면역억제제이다. Dexamethasone은 세포독성 암 치료에서 오심 방지, 정상세포의 보호와 기타 이유 등의로 빈번하게 병용처치된다. 본 연구의 목적은 간암세포주(Hep3B)에서 FK506의 항암효과와 FK506에 의한 항암효과에 대한 dexamethasone의 억제효과를 알아보기 위함이다. 세포의 손상은 세포 생존성 평가와 LDH 및 세포내 ROS 양의 측정으로 평가 하였다. 세포내 칼슘 농도([$Ca^{2+}$]i)와 JNK, Bax 단백질의 발현 정도도 평가하였다. FK506의 처치는 Hep3B의 세포사를 유도하였으며 세포생존성의 감소와 LDH, ROS 및 [$Ca^{2+}$]i 를 증가시켰다. FK506은 Bax와 JNK 의 활성을 증가시켰으며 Bcl-2의 활성을 억제하였다. Dexamethasone 처치 그 자체는 세포생존성, LDH와 ROS에 영향을 주지 않았다. 그러나 dexamethasone과 FK506의 병용처치는 FK506에 의한 LDH 방출, ROS 생성 및 JNK의 활성을 감소시켰다. 이 결과는 간암세포주에서 FK506은 항암효과를 가지지만 dexamethasone의 병용처치는 FK506에 의한 항암효과를 길항한다.