• Title/Summary/Keyword: Antibody therapy

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A Novel Monoclonal Antibody Induces Cancer Cell Apoptosis and Enhances the Activity of Chemotherapeutic Drugs

  • Xu, Heng;Tian, Yan-Na;Dun, Bo-Ying;Liu, Hai-Tao;Dong, Guang-Kuo;Wang, Jin-Hua;Lu, Shang-Su;Chen, Bo;She, Jin-Xiong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.11
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    • pp.4423-4428
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    • 2014
  • A novel monoclonal antibody (mAb), known as AC10364, was identified from an antibody library generated by immunization of mice with human carcinoma cells. The mAb recognized proteins in lysates from multiple carcinoma cell lines. Cell cytotoxicity assays showed that AC10364 significantly inhibited cell growth and induced apoptosis in multiple carcinoma cell lines, including Bel/fu, KATO-III and A2780. Compared with mAb AC10364 or chemotherapeutic drugs alone, the combination of mAb AC10364 with chemotherapeutic drugs demonstrated enhanced growth inhibitory effects on carcinoma cells. These results suggest that mAb AC10364 is a promising candidate for cancer therapy.

Simple measurement the chelator number of antibody conjugates by MALDI-TOF MS

  • Shin, Eunbi;Lee, Ji Woong;Lee, Kyo Chul;Shim, Jae Hoon;Cha, Sangwon;Kim, Jung Young
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.3 no.2
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    • pp.54-58
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    • 2017
  • Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS) is one of the powerful methods that enable analysis of small molecules as well as large molecules up to about 500,000 Da without severe fragmentation. MALDI-TOF MS, thus, has been a very useful an analytical tool for the confirmation of synthetic molecules, probing PTMs, and identifying structures of a given protein. In recent nuclear medicine, MALDI-TOF MS liner ion mode helps researcher calculate the average number of chelator(or linkage) per an antibody conjugate, such as DOTA-(or DFO-) trastuzumab for labeling a medical radioisotope. This simple technique can be utilized to improve the labeling method and control the quality at the development of antibody-based radiopharmaceuticals, which is very effected to diagnosis and therapy for in vivo tumor cells, with radioisotopes like $^{89}Zr$, $^{64}Cu$, and 177Lu. To minimize the error, MALDI-TOF MS measurement is repeatedly performed for each sample in this study, and external calibration is carried out after data collection.

Hypothyroidism Following Surgery and Radiation Therapy for Head and Neck Cancer (두경부암 환자에서 수술 및 방사선치료 후 갑상선 기능 저하)

  • Park, In-Kyu;Kim, Jae-Cheol
    • Radiation Oncology Journal
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    • v.15 no.3
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    • pp.225-231
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    • 1997
  • Purpose : Radiation therapy in combination with surgery has an important role in the therapy of the head and neck cancer We conducted a prospective study for patients with head and neck cancer treated with surgery and radiation to evaluate the effect of therapies on the thyroid gland, and to identify the factors that might influence the development of hypothyroidism. Materials and Methods : From September 1986 through December 1994, 71 patients with head and cancer treated with surgery and radiation were included in this prospective study. Patients' age ranged from 32 to 73 years with a median age of 58 years. There were 12 women and 59 men. The primary tumor sites were larynx in 34 patients, hypopharynx in 13 patients, oral cavity in 12 patients, unknown primary of the neck in 6 patients, salivary gland in 3 patients, maxillary sinus in 2 patients, and oropharynx in 1 patient. Total laryngectomy with neck dissection was carried out in 45 patients and neck dissection alone in 26 patients. All patients were serially monitored for thyroid function (T3, T4, free T4, TSH, antithyroglobulin antibody and antimicrosomal antibody) before and after radiation therapy. Radiation dose to the thyroid gland ranged from 40.6Gy to 60Gy with a median dose of 50Gy The follow-up duration was 3 to 80 months. Results :The overall incidence of hypothyroidism was 56.3\%$);7 out of 71 patients $(9.9\%)$ developed clinical hypothyroidism and 33 patients $(46.4\%)$ developed subclinical hypothyroidism. No thyroid nodules, thyroid cancers, or hyperthyroidism was detected. Hypothyroidism developed earlier in patients who underwent total laryngectomy with neck dissection than in patients with neck dissection alone (P<0.05). The risk factor that significantly influenced the incidence of hypothyroidism was a combination of surgery (total laryngectomy with neck dissection) and radiation therapy (P=0.0000), Four of 26 patients $(15.4\%)$ with neck dissection alone developed hypothyroidism while 36 of 45 patients $(80\%)$ with laryngectomy and neck dissection developed hypothyroidism. Conclusion : The hypothyroidism following surgery and radiation therapy was a relatively common complication. The factor that significantly influenced theincidence of hypothyroidism was combination of surgery and radiation therapy. Evaluation of thyroid function before and after radiation therapy with periodic thyroid function tests is recommended for an early detection of hypothyroidism and thyroid hormone replacement therapy is recommended whenever hypothyroidism develops.

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Seroprevalence of Toxoplasma gondii Infection among HIV/AIDS Patients in Eastern China

  • Shen, Guoqiang;Wang, Xiaoming;Sun, Hui;Gao, Yaying
    • Parasites, Hosts and Diseases
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    • v.54 no.1
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    • pp.93-96
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    • 2016
  • Toxoplasmosis, a neglected tropical disease caused by the protozoan parasite Toxoplasma gondii, occurs throughout the world. Human T. gondii infection is asymptomatic in 80% of the population; however, the infection is life-threatening and causes substantial neurologic damage in immunocompromised patients such as HIV-infected persons. The major purpose of this study was to investigate the seroprevalence of T. gondii infection in subjects infected with HIV/AIDS in eastern China. Our findings showed 9.7% prevalence of anti-T. gondii IgG antibody in HIV/AIDS patients, which was higher than in intravenous drug users (2.2%) and healthy controls (4.7%), while no significant difference was observed in the seroprevalence of anti-Toxoplasma IgM antibody among all participants (P>0.05). Among all HIV/AIDS patients, 15 men (7.7%) and 10 women (15.9%) were positive for anti-T. gondii IgG antibody; however, no significant difference was detected in the seroprevalence of anti-Toxoplasma IgG antibody between males and females. The frequency of anti-Toxoplasma IgG antibody was 8.0%, 13.2%, 5.5%, and 0% in patients with normal immune function ($CD4^+$ T-lymphocyte count ${\geq}500cells/ml$), immunocompromised patients (cell count ${\geq}200$ and <500 cells/ml), severely immunocompromised patients (cell count ${\geq}50$ and <200 cells/ml), and advanced AIDS patients, respectively (cell count <50 cells/ml), while only 3 immunocompromised patients were positive for anti-T. gondii IgM antibody. The results indicate a high seroprevalence of T. gondii infection in HIV/AIDS patients in eastern China, and a preventive therapy for toxoplasmosis may be given to HIV/AIDS patients based on $CD4^+$ T lymphocyte count.

Human Activated Lymphocyte Treated with Anti-CD3, CD16, CD56 Monoclonal Antibody and IL-2 (Anti-CD3, CD16과 CD56 단일항체와 IL-2를 사용하여 활성화시킨 사람의 림프구)

  • Hong, Seon-Min;Lee, Dong-Wook;Kang, Jin-Gu;Kim, Han-Soo;Cho, Sung-Hoon
    • IMMUNE NETWORK
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    • v.5 no.1
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    • pp.11-15
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    • 2005
  • Background: Throughtout the last three decades, the therapy of leukemias and lymphoma has set the stage for curative cancer therapy in systemic malignant disease. This was the result of an integrated work of basic reaserch and clinical investigators leading to more aggressive albeit tolerable protocol of chemotherapy and radiotherapy. High dose therapy marks the most elaborated strategies in this field today. However, intensification of conventional therapeutic modalities as mentioned has to be based on new approaches and the exploration of new antineoplastic mechanisms. This insight has resulted in immune therapy of cancer. Among the cells of the immune system, natural killer (NK) cells and T cells are of major interest for the development of therapeutic strategies. Methods: Cytotoxicity to target cells was measured by LDH release method, Characterization of activated lymphocyte was measured by Flow cytometry analysis. Anti-CD3, 16, 56 monoclonal antibody and IL-2 were used for the activation of NK and T cell. The analysis of effect of activated lymphocyte, in vivo, were used by Balb/c nude mouse. Results and Conclusion: Cytotoxicity to K562 cells was significantly higher in the mixture group of NK and T cells than that of a group of activating T cells. The survivors and the rate of reduction of size of tumor craft of nude mouse group treatment with activated lymphocyte was higher than that of the group without treatment with activated lymphocyte. Therefore, this results are suggested that the activated lymphocytes by anti-CD3, CD16 and CD56 can reduce the malignancy effect of lymphoma.

Evaluation of Therapeutic Effect with Serum Thyroglobulin and Whole Body Scan after 200mCi $^{131}I$ Treatment in Patients with Well-Differentiated Thyroid Carcinoma (전이성 분화 갑상선암에서 200mCi 방사성 옥소 치료효과 평가를 위한 혈청 Thyroglobulin 추적검사와 전신스캔의 의의)

  • Lee, Chang-Hee;Yoon, Jong-Kil;Jeong, Sang-Hoon;Kwu, Gyo-Seon;Choi, Chang-Woon;Lim, Sang-Moo;Hong, Sung-Woon
    • The Korean Journal of Nuclear Medicine
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    • v.29 no.4
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    • pp.451-459
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    • 1995
  • Thirty-eight patients with metastatic well-differentiated thyroid carcinoma treated with 200mCi $^{131}I$ were studied. There were false negative serum thyroglobulin values during TSH suppression or at anti-thyroglobulin antibody(+) and discrepancies between findings of whole body scan and serum thyroglobulin level. After one to five cycles of 200mCi $^{131}I$ therapy, complete remission and partial remission were achieved at 5.3% and 57.9%, respectively. We concluded that all of serum thyroglobulin, TSH, anti-thyroglobulin antibody, $^{131}I$ or $^{123}I$ whole body scan were necessary in follow up of metastatic well-differentiated thyroid carcinoma. Also, if there was no response after repetitive 200mCi $^{131}I$ therapy, higher doses of $^{131}I$ therapy should be considered.

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Methods for rapid identification of a functional single-chain variable fragment using alkaline phosphatase fusion

  • Lee, Kyung-Woo;Hur, Byung-Ung;Song, Suk-Yoon;Choi, Hyo-Jung;Shin, Sang-Hoon;Cha, Sang-Hoon
    • BMB Reports
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    • v.42 no.11
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    • pp.731-736
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    • 2009
  • The generation of functional recombinant antibodies from hybridomas is necessary for antibody engineering. However, this is not easily accomplished due to high levels of aberrant heavy and light chain mRNAs, which require a highly selective technology that has proven complicated and difficult to operate. Herein, we attempt to use an alkaline phosphate (AP)-fused form of single-chain variable fragment (scFv) for the simple identification of a hybridoma-derived, functional recombinant antibody. As a representative example, we cloned the scFv gene from a hybridoma-producing mouse IgG against branched-chain keto acid dehydrogenase complex-E2 (BCKD-E2) into an expression vector containing an in-frame phoA gene. Functional recombinant antibodies were easily identified by conventional enzyme-linked immunosorbent assay (ELISA) by employing scFv-AP fusion protein, which also readily serves as a valuable immuno-detective reagent.

Isolation and Characterization of Human scFv Molecules Specific for Recombinant Human Heat Shock Protein (HSP) 70.1

  • Baek, Hyun-jung;Lee, Jae-seon;Seo, Jeong-sun;Cha, Sang-hoon
    • IMMUNE NETWORK
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    • v.4 no.1
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    • pp.7-15
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    • 2004
  • Background: The heat shock proteins (HSPs) play an important role in cellular protection mechanisms against physical or chemical stresses. In this study scFv antibodies specific for human HSP70.1 were isolated from a semi-synthetic human scFv library with the ultimate goal of developing anti-HSP70.1 intracellular antibody (intrabody) that may offer an attractive alternative to gene targeting to study the function of the protein in cells. Methods: A semi-synthetic human scFv display library ($5{\times}10^{8}$ size) was constructed using pCANTAB-5E vector and the selection of the library against bacterially expressed recombinant human HSP70.1 was attempted by panning. Results: Three positive clones specific for recombinant HSP70.1 were identified. All three clones used $V_{H}$ subgroup III. On the other hand, $V_{L}$ of two clones belonged to the kappa light chain subgroup I, but the other utilized $V_{k}$ subgroup IV Interestingly, these scFv molecules specifically reacted to the recombinant HSP70.1, yet failed to recognize native HSP70 induced in U937 human monocytic cells by heat treatment. Conclusion: Our results indicated that affinity selection of an scFv phage display library using recombinant antigens produced in E. coli might not guarantee the isolation of scFv antibody molecules specific for a native form of the antigen. Therefore, the source of target antigens needs to be chosen carefully in order to isolate biofunctional antibody molecules.

Resurrection of antibody as a therapeutic drug (항체 : 치료제로서의 부활)

  • Chung, Hong Keun;Chung, Junho
    • IMMUNE NETWORK
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    • v.1 no.1
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    • pp.7-13
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    • 2001
  • Currently 18 monoclonal antibodies were approved by FDA for inj ection into humans for therapeutic or diagnostic purpose. And 146 clinical trials are under way to evaluate the efficacy of monoclonal antibodies as anti-cancer agents, which comprise 9 % of clinical trials in cancer therapy field. When considering a lot of disappointment and worries existed in this field during the past 15 years, this boom could be called as resurrection. Antibodies have several merits over small molecule drug. First of all it is easier and faster in development, as proper immunization of the target proteins usually raises good antibody response. The side effects of antibodies are more likely to be checked out in immunohistomchemical staining of whole human tissues. Antibody has better pharmacokinetics, which means a longer half-life. And it is non-toxic as it is purely a "natural drug. Vast array of methods was developed to get the recombinant antibodies to be used as drug. The mice with human immunoglobulin genes were generated. Fully human antibodies can be developed in fast and easy way from these mice through immunization. These mice could make even human monoclonal antibodies against any human antigen like albumin. The concept of combinatorial library was also actively adopted for this purpose. Specific antibodies can be screened out from phage, mRNA, ribosomal library displaying recombinant antibodies like single chain Fvs or Fabs. Then the coding genes of these specific antibodies are obtained from the selected protein-gene units, and used for industrial scale production. Both $na\ddot{i}ve$ and immunized libraries are proved to be effective for this purpose. In post-map arena, antibodies are receiving another spotlight as molecular probes against numerous targets screened out from functional genomics or proteomics. Actually many of these antibodies used for this purpose are already human ones. Through alliance of these two actively growing research areas, antibody would play a central role in target discovery and drug development.

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