• BMB Reports
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• 제28권6호
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• pp.556-561
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• 1995

The purpose of this study was to establish an in vitro culture method of tumor-specific T cells, and determine the efficacy of the cultured tumor-specific cytotoxic T-lymphocytes (CTL) as an agent of anti-tumor immunotherapy against a murine lymphoma, TIMI.4. Tumor-specific T-lymphocytes derived from C57BL/6 mice (thy-1.2) immune to TIMI.4 were activated by in vitro stimulation with the irradiated TIMI.4 cells, and expanded by restimulation with TIMI.4 in the presence of the concanavalin A-stimulated rat spleen culture supernatant, and splenic antigen-presenting cells. In vitro restimulation enhanced markedly the proportion of $CD8^+$, a predominant surface marker of CTL and the cytotoxic activity in the cultured immune T cell population. The resulting TIMI.4-specific T cells were adoptively transferred into nude mice. The tumor cells residing in the host after 7 days of adoptive transfer to B6.PL (thy-1.1) mice were quantified by use of an antibody directed to the thy-1.2 allele. The TIMI.4 cells in the recipient nude mice were decreased in a dose-dependent manner. Anti-tumor activity of the TIMI.4-specific T cells was also demonstrated by a survival test, where the tumor-bearing nu/nu mice which received the activated T-cells survived about 30% longer than the control mice which received the tumor cells alone. These suggest that adoptive transfer of TIMI.4-specific T cells could be a candidate for effective therapy of the murine lymphoma.

• IMMUNE NETWORK
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• 제4권2호
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• pp.88-93
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• 2004

Background: Bone marrow mesenchymal stem cells (MSC) inhibit the immune response of lymphocytes to specific antigens and dendritic cells (DC) are professional antigenpresenting cells whose function is to present antigen to naive T-lymphocytes with high efficiency and play a central role in the regulation of immune response. We studied the effects of MSC on DC to evaluate the relationship between MSC and DC in transplantation immunology. Methods: MSC were expanded from the bone marrow and DC were cultured from peripheral blood mononuclear cells (PBMNC) of 6 myelogenous leukemia after achieving complete response. Responder cells isolated from PBMNC and lysates of autologous leukemic cells are used as tumor antigen. The effect of MSC on the DC was analyzed by immunophenotype properties of DC and by proliferative capacity and the amount of cytokine production with activated PBMNC against the allogeneic lymphocytes. Also, cytotoxicity tests against leukemic cells studied to evaluate the immunologic effect of MSC on the DC. Results: MSC inhibit the CD83 and HLA-class II molecules of antigen-loaded DC. The proliferative capacity and the amount of INF-$\gamma$ production of lymphocytes to allogeneic lymphocytes were decreased in DC co-cultured with MSC. Also the cytotoxic activity of lymphocytes against leukemic cells was decreased in DC co-cultured with MSC. Conclusion: MSC inhibit the activation and immune response of DC induced by allogeneic or tumor antigen.

• 대한핵의학회지
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• 제24권1호
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• pp.29-36
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• 1990

Most of the diagnostic methods currently used for the detection of neoplastic masses provide indirect evidence. To obtain greater specificity in the interpretation of neoplasias by in vivo methods, the immunological approach appears to be most promising. Two problems that interfered with progress in this field were the lack of tumor specific antigen and the lack of well-defined and reproducible antibodies. To improve the sensitivity and specificity of radioimmunoscintigraphy as a technique for tumor localization, the use of monoclonal antibodies, fragments of antibodies and single photon emission computerized tomography (SPECT) are reasonable. The obvious advantages of monoclonal antibodies are their homogeneity, their specificity for the immunizing antigen and the reaction with a single determinant-thus no large immunecomplexes with antigen are formed. Monoclonal antibody technique has recently provided an opportunity to reevaluate the role of nuclear medicine for the diagnosis of malignant diseases by using the immunological approach. Out first results by means of radioimmunoscintigraphy of CEA and CA 19-9 producing tumors using a cocktail of fragments F $(ab')_2$, of mocolonal antibodies to CA 19-9 and CEA labeled with $^{131}I$ (IMACIS-1) are reported. The aims of this investigation was to evaluate the role of immunoscintigraphy in patients with colorectal and other cancers for diagnosis of local recurrences and metastasis. This report contains results of the first 8 colorectal and pancreas cancer patients with the elevation of the level of serum CEA and/or CA 19-9. IMACIS-1 was injected intravenously during 30 minutes in 100 ml saline solution after skin test. Planar scintigrams were recorded 3, 5 and 7 days after the injection of the IMACIS-1. Anterior, lateral and posterior views of the liver as well as anterior and posterior views of the pelvis were obtained in each patients as an $^{131}I-antibody$ image. We were able to localize exactly the malignant process with the double-nuclide double-compound $^{99m}Tc\;^{131}I$ (Tc+l) scintigrams. In Tc & I double-nuclide scintigraphy, computer subtraction display provided more clear localization of the tumor. We compared the results of radioimmunoscintigraphy with CT, ultrasonograms, conventional scintigrams. The results were as follows: 1) The sensitivity and specificity of radioimmunoscintigraphy using the fragments $F(ab')_2$ of the cocktails of CEA and CA 19-9 monoclonal antibodies were 80% and 100% respectively. 2) Tumor detection rate was not proportionated to the level of serum tumor markets. 3) Second tracer technique was essential for tumor localization as an anatomic landmark using double-nuclide scintigraphy. 4) A slow infusion of the antibodies was necessary to prevent the formation of large immune complexes. 5) Tumor/non-tumor radioactivity was most elevated at 7 days delayed imaging. 6) Using planar scintigraphic technique of $^{131}I$ labeled monoclonal antibodies are possible for imaging most of the tumors.

• Journal of Yeungnam Medical Science
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• 제23권1호
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• pp.90-95
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• 2006

결합조직형성소원형세포종양은 매우 드문 악성 연부조직 종양으로 소아와 청소년기에 복강과 골반강 내에 주로 발생한다. 저자들은 복강에 발생한 결합조직형성소원형세포종양 1예를 경험하였기에 문헌 고찰과 함께 보고한다. 50세 남자가 2개월간의 복부 불쾌를 주소로 내원하였다. 방사선 소견에서 오른쪽 복강 내에 종괴가 관찰되었다. 절제된 종괴는 크기가 $14.0{\times}12.5{\times}8.5cm$ 이며, 회백색을 띠었으며 가로 잘록창자의 장막에 붙어 있었다. 조직학적으로 종괴는 결합조직을 형성하는 기질 내에 작고 둥근 핵을 가진 종양세포들의 증식이 보였다.

• Journal of Digestive Cancer Research
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• 제5권1호
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• pp.55-57
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• 2017

A 64-year-old man was admitted due to jaundice for 2 weeks. Radiologic findings revealed biliary stricture at the hepatic hilum with intrahepatic duct dilation suggesting Bismuth type IV Klatskin tumor. Jaundice improved spontaneously several days after hospitalization. Surgical treatment was considered but he only wanted to observe without specific treatment. Ten months later, he was re-admitted due to the recurrence of jaundice. Computed tomography (CT) showed no significant difference compared to previous results. Serum cancer antigen 19-9 and Immunoglobulin G4 were normal. Endoscopic forcep biopsy during endoscopic retrograde cholagiopancreatography (ERCP) revealed chronic inflammation. After steroid use under possible diagnosis of IgG4 related cholangiopathy, biliary stricture improved slightly. Four years later, he was hospitalized with the occurrence of acute cholangitis. Endoscopic retrograde biliary drainage was performed following endobiliary forcep biopsy. Pathology revealed well-differentiated adenocarcinoma at this time. Combined chemotherapy based on gemcitabine and cisplatin was performed. Six months later, CT revealed partial response.

• IMMUNE NETWORK
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• 제22권1호
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• pp.4.1-4.22
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• 2022

In the era of immunotherapeutic control of cancers, many advances in biotechnology, especially in Ab engineering, have provided multiple new candidates as therapeutic immuno-oncology modalities. Bispecific Abs (BsAbs) that recognize 2 different antigens in one molecule are promising drug candidates and have inspired an upsurge in research in both academia and the pharmaceutical industry. Among several BsAbs, T cell engaging BsAb (TCEB), a new class of therapeutic agents designed to simultaneously bind to T cells and tumor cells via tumor cell specific antigens in immunotherapy, is the most promising BsAb. Herein, we are providing an overview of the current status of the development of TCEBs. The diverse formats and characteristics of TCEBs, in addition to the functional mechanisms of BsAbs are discussed. Several aspects of a new TCEB-Blinatumomab-are reviewed, including the current clinical data, challenges of patient treatment, drawbacks regarding toxicities, and resistance of TCEB therapy. Development of the next generation of TCEBs is also discussed in addition to the comparison of TCEB with current chimeric antigen receptor-T therapy.

• Biomolecules & Therapeutics
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• 제32권5호
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• pp.556-567
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• 2024

β-glucan, a polysaccharide found in various sources, exhibits unique physicochemical properties, yet its high polymerization limits clinical applications because of its solubility. Addressing this limitation, we introduce PPTEE-glycan, a highly purified soluble β-1,3/1,6-glucan derived from Aureobasidium pullulans. The refined PPTEE-glycan demonstrated robust immune stimulation in vitro, activated dendritic cells, and enhanced co-stimulatory markers, cytokines, and cross-presentation. Formulated as a PPTEE + microemulsion (ME), it elevated immune responses in vivo, promoting antigen-specific antibodies and CD8+ T cell proliferation. Intratumoral administration of PPTEE + ME in tumor-bearing mice induced notable tumor regression, which was linked to the activation of immunosuppressive cells. This study highlights the potential of high-purity Aureobasidium pullulans-derived β-glucan, particularly PPTEE, as promising immune adjuvants, offering novel avenues for advancing cancer immunotherapy.

• Tuberculosis and Respiratory Diseases
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• 제72권6호
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• pp.507-510
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• 2012

Carbohydrate antigen 19-9 (CA19-9) is a specific tumor marker of the biliary, pancreatic and gastrointestinal tracts. CA19-9 is occasionally elevated in serum in patiens with benign pulmonary diseases such as bronchiectasis, idiopathic interstitial pneumonia or collagen disease-associated pulmonary fibrosis. Intralobar pulmonary sequestration is an uncommon congenital lung anomaly. It is dissociated from the normal tracheobronchial tree and is supplied by an anomalous systemic artery. There have been some reports of elevation of CA19-9 in this lesion. We report a case of intralobar pulmonary sequestration with elevated serum CA19-9 in a 29-year-old man who was diagnosed with bronchiectasia of left lower lung field on general check up. He had no evidence of any malignant disease in pancreatobiliary or gastrointestinal tracts. Elevated serum CA19-9 level might be encountered with benign pulmonary disease such as pulmonary sequestration.

• Asian Pacific Journal of Cancer Prevention
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• 제15권9호
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• pp.3927-3932
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• 2014

Background: Epidermal growth factor receptor (EGFR) mutations and echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) define specific molecular subsets of lung adenocarcinomas with distinct clinical features. Our purpose was to analyze clinical features and prognostic value of EGFR gene mutations and the EML4-ALK fusion gene in lung adenocarcinoma. Patients and Methods: EGFR gene mutations and the EML4-ALK fusion gene were detected in 92 lung adenocarcinoma patients in China. Tumor marker levels before first treatment were measured by electrochemiluminescence immunoassay. Results: EGFR mutations were found in 40.2% (37/92) of lung adenocarcinoma patients, being identified at high frequencies in never-smokers (48.3% vs. 26.5% in smokers; P=0.040) and in patients with abnormal serum carcinoembryonic antigen (CEA) levels before the initial treatment (58.3% vs. 28.6%, P=0.004). Multivariate analysis revealed that a higher serum CEA level before the initial treatment was independently associated with EGFR gene mutations (95%CI: 1.476~11.343, P=0.007). We also identified 8 patients who harbored the EML4-ALK fusion gene (8.7%, 8/92). In concordance with previous reports, younger age was a clinical feature for these (P=0.008). Seven of the positive cases were never smokers, and no coexistence with EGFR mutation was discovered. In addition, the frequency of the EML4-ALK fusion gene among patients with a serum CEA concentration below 5ng/ml seemed to be higher than patients with a concentration over 5ng/ml (P=0.021). No significant difference was observed for time to progression and overall survival between EML4-ALK-positive group and EML4-ALK-negative group or between patients with and without an EGFR mutation. Conclusions: The serum CEA level before the initial treatment may be helpful in screening population for EGFR mutations or EML4-ALK fusion gene presence in lung adenocarcinoma patients.

• Journal of Microbiology
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• 제39권4호
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• pp.300-304
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• 2001

Epstein-Barr Virus(EBV)-transformed lymphoblastoid B cell lines, BLCL which expresse antigens, are potential antigen-presenting cells(APCs) for the induction of CTL in vitro. However transfection of BLCLs with subsequent selection by antibiotics is notoriously difficult because plating efficiencies of BLCLsare reported to be 1% or less. To generated stable transfectants of BLCLs we produced high titers of retroviruess encoding pp 65 antigen of human cytomegalovirus of foreign antigens and trans-duced them of BLCLs. The pp 65 gene was cloned into the retroviral vector pLXSN. The recombinant retroviral vector was transfected to ecotropic packaging cell line, CP&E86, and this polyclonal recom-binant retrovirus was transduced to PA317 that is amphotropic pakaging cell line. The titers of colned PA317 amphotropic retroviruses ranged from 5 to $\times$10$^{6}$ colony forming units (CFU)per ml (CFU/ml) We performed three rounds of consecutive transductions to BLCLs in order to improve the clon-ing effieiencies. The expression of recombinant HCMV-pp65 antigen was more than 20% after the final transduction. THe third-transduced BLCLs were easily selected in optimal concentration of G418. BLCLs expressing foreign antigens could be used as target cells for CTL assay and/or as APCs for induction of in vitro CTL responses specific for viral and tumor antigens.