• IMMUNE NETWORK
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• 제1권3호
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• pp.250-259
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• 2001

To determine if initial infection with Mycobacterium tuberculosis changes the balance of cytokines between T cells and macrophages, we evaluated interferon (IFN)-${\gamma}$), interleukin-12 (IL)-12, and tumor necrosis factor (TNF)-${\alpha}$ productions by peripheral blood mononuclear cells (PBMC) from 15 untreated active pulmonary tuberculosis (TB) patients and 12 healthy tuberculin reactors (HTR). Freshly isolated PBMC were stimulated with Triton X-100 solubilized protein (TSP), 30-kDa or purified protein derivatives (PPD) antigen for 6, 18 and 96 hours. IL-12 p40 production by antigen-stimulated PBMC from TB patients was significantly decreased compared with that in HTR. In addition, IFN-${\gamma}$ production was significantly depressed in TB patients than that in HTR at a 96-hr stimulation. However, TNF-${\alpha}$ production was significantly higher in antigen-stimulated PBMC from TB than that of HTR. A pronounced increase in IFN-${\gamma}$ protein followed neutralization of IL-10 in early TB patients. However, neutralization of TNF-${\alpha}$ did not significantly alter IFN-${\gamma}$ induction in PBMC from TB patients. There were no significantly differences in the cytokine productions among three proteins, TSP, 30-kDa or PPD antigen. These results indicate that development of TB may be strongly associated with dysregulated productions of IL-12, IFN-${\gamma}$ and TNF-${\alpha}$, during the initial immune responses to M. tuberculosis. Further understanding of operative cytokine networks during human immune cell responses to protein antigens of M. tuberculosis may improve strategies for vaccine development.

• 치과방사선
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• 제27권2호
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• pp.63-81
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• 1997

This study was performed in order to identify changes of the plasma membrane proteins in rat submandibular gland tumors induced by 7,12-dimethylbenz[a]anthracene [DMBA] and X-irradiation. Two kinds of tumor associated membrane proteins (protein A and B) were isolated with 3 M KCl extraction from rat submandibular gland tumors induced by DMBA and X-irradiation. To identify their antigenicities, immunoelectrophoresis and double immunodiffusion was carried out with various proteins extracted from liver, heart, skin and pancreas of adult rats and from embryonic liver, heart and skin. The rabbit antisera against the protein A did not cross-react with any of the proteins extracted from the above mentioned tissues, suggesting that protein A might be tumor specific antigen. However, the rabbit antisera against protein B was precipitated with proteins extracted from the liver of adult and embryonic rats. Polyacrylamide gel electrophoresis of these two proteins (A and B) showed that protein A was a dimer with molecular weights of 69,000 and 35,000 dalton, whereas protein B was a monomer with molecular weight of 50,000 dalton.

• Parasites, Hosts and Diseases
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• 제52권6호
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• pp.605-612
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• 2014

Toxoplasma gondii is an intracellular protozoan parasite that causes a Th1 cellular immunity. Our previous study showed that T. gondii lysate antigen (TLA) treatment in S180 tumor-bearing mice resulted in tumor reduction by suppressing CD31 expression, a marker of angiogenesis. In the present study, to investigate tumor suppressive effect of TLA under the absence of T lymphocytes, athymic nude mice were compared with euthymic mice in the anti-tumorigenic effect triggered by TLA in CT26 tumors. According to the results, intratumorally injected TLA reduced tumor growth and TIMP-1 level, a metastatic marker, in both euthymic and athymic mice. TLA treatment led to a sharp increase in IL-12 expression in serum cytokine profiling of athymic mice, and increased MyD88 signals in macrophages derived from the bone marrow, implying the activation of innate immunity. The selective induction of IL-12 by TLA treatment had an anti-tumorigenic effect.

• Parasites, Hosts and Diseases
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• 제47권2호
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• pp.175-177
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• 2009

Cancer is the main cause of death in developed countries. However, in underdeveloped countries infections and parasitic diseases are the main causes of death. There are raising scientific evidences indicating that parasitic infections induce antitumor activity against certain types of cancers. In this study, the effects of Toxoplasma gondii and Toxocara canis egg antigens in comparison with Bacillus Calmette Guerin (BCG) (known to have anticancer distinctive) on WEHI-164 fibosarcoma transplanted to BALB/c mice was investigated. Groups of 6 male BALB/c mice injected with T. gondii antigen, BCG, or T. canis egg antigen as case groups and alum alone as control groups. All mice were then challenged with WEHI-164 fibrosarcoma cells. The mice were examined for growth of the solid tumor and the tumor sizes were measured every other day up to 4wk. The mean tumor area in T. gondii, BCG, or alum alone injected mice in 4 different days of measurements was $25\;mm^2$, $23\;mm^2$, and $186\;mm^2$ respectively, Also the mean tumor area in T. canis injected mice in 4 different days was $25.5\;mm^2$ compared to the control group (alum treated) which was $155\;mm^2$. T. gondii parasites and T. canis egg antigens induced inhibition of the tumor growth in the fibrosarcoma mouse model. We need further study to clarify the mechanisms of anti-cancer effects.

• IMMUNE NETWORK
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• 제22권1호
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• pp.6.1-6.19
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• 2022

Chimeric antigen receptor (CAR) T cells, which express a synthetic receptor engineered to target specific antigens, have demonstrated remarkable potential to treat haematological malignancies. However, their transition beyond haematological malignancy has so far been unsatisfactory. Here, we discuss recent challenges and improvements for CAR T cell therapy against solid tumors: Antigen heterogeneity which provides an effective escape mechanism against conventional mono-antigen-specific CAR T cells; and the immunosuppressive tumor microenvironment which provides physical and molecular barriers that respectively prevent T cell infiltration and drive T cell dysfunction and hypoproliferation. Further, we discuss the application of CAR T cells in infectious disease and autoimmunity.

• 생명과학회지
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• 제16권6호
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• pp.904-910
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• 2006

수지상세포는 종양면역에서 필수적인 강력한 CTL 반응을 개시할 수 있는 유일한 세포이다 . 특히 외인성 종양항원에 대한 CTL 반응 유도는 활성화된 수지상세포의 IL-12 분비를 통한 CD4+ helper T세포의 cross-priming을 필요로 한다. 그러나 최근에 활성화된 수지상세포는 $Th_1$ 면역반응을 유도하지만 활성화 시간이 경과함에 따라 오히려 $Th_2$반응을 유도 할 수 있다. 따라서 본 연구에서는 OVA를 종양항원 모델로 설정하여 종양특이적인 CTL 반응을 형성하기 위한 최적의 수지상세포 활성화 조건을 조사하였다. 마우스 골수세포에 서 수지상세포로의 분화는 항원제시 기능을 위한 표면분자의 발현 측면에서 볼 때 배양 6일-7일 정도가 적합하였다. 수지상세포의 IL-12 생성능은 배양 6일 이상, OVA 항원 탑재 8시간 이상의 경우에 연이은 LPS 성숙자극으로 오히려 감소하는 경향을 보였다. 즉 배양 6일의 수지상세포에 OVA 항원 탑재를 8시간 수행한 경우(8-h DC)가 in vitro에서의 IL-12생성능, ex vivo에서의 세포내 $IFN-{\gamma}$를 발현하는 CD8+ T세포의 증가 및 OVA 특이적인 세포독성효과 등에서 가장 좋은 결과를 보였다. 또한 in vivo에서 종양 치료 및 예방효과에서도 8-h DC로 면역한 경우에 가장 우수한 종양형성 억제 효과와 생존기간 연장효과를 보였다. 현재 대부분의 수지상 세포를 이용한 항종양 백신에서 항원 탑재반응을 24시간 동안 수행하고 있으나, 본 실험의 결과로 볼 때, 8시간의 in vitro 항원 탑재가 보다 효과적인 종양특이적 CTL 반응과 항종양 면역반응을 유도함을 알 수 있다. 결론적으로 본 연구를 통하여 8시간 이상의 항원접촉은 수지상세포의 기능적 활성능력을 오히려 고갈시킬 수 있음을 제시한다.

• 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.

• 생명과학회지
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• 제21권6호
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• pp.912-922
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• 2011

Cancer-testis (CT) antigen은 다양한 종양과 정상 고환에서 제한적으로 발현되고, 암환자에서 체액성 면역과 세포성 면역반응을 일으키는 종양항원이다. 지금까지 MAGE, NY-ESO-1, GAGE, BAGE, LAGE, SSX2, NY-SAR-35를 포함하여 100개 이상의 CT antigen들이 동정되었고, 이러한 CT antigen들은 백신을 이용한 면역치료에 있어서 중요한 요소로 작용할 것으로 사료된다. CT antigen은 여러 가지 방법들을 통해 확인할 수 있고, X 염색체에 암호화 되어있는 CT-X gene과 X 염색체에 암호화 되어있지 않은 non-X CT gene으로 나눌 수 있다. 또한 몇몇의 종양에서 비정상적으로 활성화되지 않거나 발현되지 않는 CT antigen도 존재한다. 생식세포 조직과 종양에서 CT-X gene의 생물학적 역할이 아직 명확하게 규명되지 않았지만, 현재 여러 종류의 CT antigen을 이용한 암백신 치료법이 시도되고 있다. 본 논문은 암의 면역치료를 위한 CT antigen의 최근 연구동향과 앞으로의 연구방향에 대해 서술하고자 한다.

• Tuberculosis and Respiratory Diseases
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• 제39권5호
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• pp.400-406
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• 1992

연구배경 : 최근 연구가 활발한 SCC 항원을 이용하여 폐암환자의 진단적 의미, 치료효과 판정, 예후를 예측할 수 있는 지표로써의 가능성을 알아보고자 본 연구를 시행하였다. 방법 : 정상대조군, 양성 폐질환 환자군과 폐암환자에서 SCC 항원을 측정하였으며 폐암 환자를 대상으로 치료전과 치료후 SCC Riabeap radioimmunoassay kit를 이용하여 SCC 항원을 측정하였다. 결과 : 1) SCC 항원치는 편평세포 폐암환자인 경우 $2.26{\pm}1.53\;ng/ml$, 기타 폐암은 $0.62{\pm}0.53\;ng/ml$, 양성 폐질환 환자는 $0.67{\pm}0.38\;ng/ml$, 정상 대조군은 $0.53{\pm}0.36\;ng/ml$ 이었다. 2) SCC 항원이 양성을 보인 편평세포 폐암환자는 42%(5/12)이었고 기타 폐암환자 양성 폐질환환자, 정상 대조군은 1명도 없었다. 3) 편평 세포폐암 환자의 SCC 항원 평균치는 병기에 따라 I기에 $2.07{\pm}1.56\;ng/ml$, $III_a$기는 $5.04{\pm}0.53\;ng/ml$, $III_b$기는 $1.94{\pm}0.7\;ng/ml$, IV기는 $1.07{\pm}0.64\;ng/ml$ 이었다. 4) 치료에 따른 항원역가는, 치료에 반응을 보인 환자에게서 치료 전보다 치료후 유의하게 감소하는 것을 볼 수가 있었다. 결론 : 이상의 결과로 SCC 항원은 편평세포 폐암을 진단하는 보조적인 수단으로서 이용 가능성과 치료에 따른 효과를 판정할 수있는 추적검사 방법으로서의 가능성을 제시하였다.

• 대한핵의학회지
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• 제29권3호
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• pp.332-342
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• 1995

This study was designed to evaluate the effects of various factors on the therapeutic effect of the I-131 labeled anti-carcinoembryonic antigen monoclonal antibody(anti-CEA antibody). Tetrazolium-based colorimetric assay (MTT) was used to compare in vitro cytotoxicity of 3 Korean colon cancer cell lines (SNU-C2A, SNU-C4, SNU-C5) for selection of proper 2 cell lines in this study. The changes of the size of tumor which was xenografted to nude mice (balb/c nu/nu) were compared in 4 groups (group treated I-131 labeled anti-CEA antibody, group treated with non-radiolabeled anti-CEA antibody, group treated with I-131 labeled anti-human chorionic gonadotropin monoclonal antibody (anti-hCG antibody) as nonspecific antibody, and group injected with normal saline as a control). Immunohistochemical staining and in vivo autoradiography were performed after excision of the xenografted tumor. The results were as below mentioned. The in vitro cytotoxic effect of I-131 labeled anti-CEA antibody is most prominent in SNU-C5 cell line between 3 cancer cell lines. The changes of xenografted tumor size in both SNU-C4 and SNU-5S cell tumors at the thirteenth day after injection of the antibodies were smallest in the group treated with I-131 labeled anti-CEA antibody (SNU-C4/SNU-C5; 324/342%) comparing with other groups, group treated with anti-CEA antibody (622/660%), group treated with I-131 anti-hCG antibody (538/546%), and control group(1030/724%)(P<0.02 in SNU-C4 and P<0.1 in SNU-C5 at the 13th day after injection of antibodies). On the thirteenth day after injection of the antibodies nude mice were sacreficed to count the radiouptake of tumor and to check the changes of tumor size. Correlations between radiouptake and change of tumor size were calculated in each groups and significant negative correlation was only obtained in the group treated with I-131 anti-CEA antibody (p<0.05). There were no correlations between antigenic expression of carcinoembryonic antigen and distribution of anti-CEA antibody in both SNU-C4 and SNU-C5 cell tumors on immunoperoxidase staining. On in vivo autoradiography the distributions of anti-CEA antibody were heterogeneous and the intensities of binding were various in SNU-C4 and SNU-C5 cell tumors. It is concluded that I-131 labeled tumor-specific monoclonal antibody, anti-CEA antibody is effective in suppressing the xenografted tumor growth and the effect is influenced by sensitivity of tumor cell itself to the radiolabeled antibody and other local factors instead of specificity of antibody.