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Identification of a gene engineering antibody against cystic echinococcosis in liver
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作者 Xin-Hua Chen Hao Wen +3 位作者 Yao-Xin Zhang Xiao-Hui Feng Xiao-Mei Lu Dong Ma the Xinjiang Hydatid Clinical Research Institute and the Department of Infectious Diseases First Teaching Hospital, Xinjiang Medical University, Urumqi 830054, China 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS 2003年第3期383-386,共4页
OBJECTIVE: To identify a gene engineering antibody against cystic echinococcosis in liver. METHODS: A single chain of variable fragment of human antibodies (ScFvs) was selected from the library by using affinity selec... OBJECTIVE: To identify a gene engineering antibody against cystic echinococcosis in liver. METHODS: A single chain of variable fragment of human antibodies (ScFvs) was selected from the library by using affinity selection technique with the recombinant antigen on solid surface. The positive clones were demonstrated by ELISA and their DNA sequences were also determined. RESULTS: The DNA sequence data showed that the antibody gene is composed of 768bp. In addition, a specific combination capacity with recombinant Echinococcus granulosus antigen B (r-EgB) was demonstrated by ELISA. CONCLUSION: The obtained gene engineering antibody against r-EgB may have potential implications in immunological treatment and drug targeting delivery. 展开更多
关键词 cystic echinococcosis in liver gene engineering antibody phage display single chain of varlable fragment of human antibody recombinant Echinococcus granulosus antigen B
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Improving antibody affinity through in vitro mutagenesis in complementarity determining regions
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作者 Wei Ye Xiaoyu Liu +12 位作者 Ruiting He Liming Gou Ming Lu Gang Yang Jiaqi Wen Xufei Wang Fang Liu Sujuan Ma Weifeng Qian Shaochang Jia Tong Ding Luan Sun Wei Gao 《The Journal of Biomedical Research》 CAS CSCD 2022年第3期155-166,共12页
High-affinity antibodies are widely used in diagnostics and for the treatment of human diseases.However,most antibodies are isolated from semi-synthetic libraries by phage display and do not possess in vivo affinity m... High-affinity antibodies are widely used in diagnostics and for the treatment of human diseases.However,most antibodies are isolated from semi-synthetic libraries by phage display and do not possess in vivo affinity maturation,which is triggered by antigen immunization.It is therefore necessary to engineer the affinity of these antibodies by way of in vitro assaying.In this study,we optimized the affinity of two human monoclonal antibodies which were isolated by phage display in a previous related study.For the 42A1 antibody,which targets the liver cancer antigen glypican-3,the variant T57H in the second complementarity-determining region of the heavy chain(CDR-H2)exhibited a 2.6-fold improvement in affinity,as well as enhanced cell-binding activity.For the I4A3 antibody to severe acute respiratory syndrome coronavirus 2,beneficial single mutations in CDR-H2 and CDR-H3 were randomly combined to select the best synergistic mutations.Among these,the mutation S53P-S98T improved binding affinity(about 3.7 fold)and the neutralizing activity(about 12 fold)compared to the parent antibody.Taken together,single mutations of key residues in antibody CDRs were enough to increase binding affinity with improved antibody functions.The mutagenic combination of key residues in different CDRs creates additive enhancements.Therefore,this study provides a safe and effective in vitro strategy for optimizing antibody affinity. 展开更多
关键词 antibody engineering phage display affinity maturation
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GENE ENGINEERING EB VIRUS MEMBRANE ANTIGEN IN DETECTION OF MA-IgA ANTIBODY(COMPARISON WITH VCA-IgA AND EA-IgA ANTIBODIES)
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作者 刘孟忠 李振权 皮国华 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 1991年第2期33-36,共4页
With gene engineering EB virus membrane antigen as the diagnostic antigen, indirect immunofluo-rescence (IF) assay was used to detect IgA antibody against EB virus membrane antigen (MA-IgA) in sera from 202 nasopharyn... With gene engineering EB virus membrane antigen as the diagnostic antigen, indirect immunofluo-rescence (IF) assay was used to detect IgA antibody against EB virus membrane antigen (MA-IgA) in sera from 202 nasopharyngeal carcinoma (NPC) patients and 315 controls (normal and patients with other tumors). MA-IgA antibody was positive in 96.8% of the pretreatment NPC patients with a GMT of 1:36.3. MA-IgA detection by this method was more sensitive than EA-IgA detection by IE. In contrast, patients with tumors other than NPC were negative for MA-IgA antibody. 9.1% of VCA-IgA positive persons were MA-IgA positive with a GMT of less than 1:5. No MA-IgA positive was found in VCA-IgA negatives. The results indicated that this method was relatively specific. In the treatment group, the positive rate and GMT of MA-IgA antibody declined with increase in survival time and the decline was faster than VCA-IgA. When recurrence or distant metastasis developed, similar to VCA-IgA and EA-IgA antibodies, the positive rate and GMT of MA-IgA antibody increased to its pretreatment level. Therefore, MA-IgA detection might be valuable in the early diagnosis and monitor of NPC. 展开更多
关键词 IgA COMPARISON WITH VCA-IgA AND EA-IgA ANTIBODIES GENE ENGINEERING EB VIRUS MEMBRANE ANTIGEN IN DETECTION OF MA-IgA antibody VCA MA EA
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Recombinant Human IgG antibodies against Human Cytomegalovirus 被引量:1
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作者 TAO DUAN XIAO-FANG WANG +2 位作者 SHU-YUAN XIAO SHU-YAN GU AND MI-FANG LIANG 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2008年第5期372-380,共9页
Objective To study the passive immunization with human monoclonal antibodies as for prophylaxis of human cytomegalovirus (HCMV) infection. Methods Fab monoclonal antibodies to HCMV were recovered by repertoire cloni... Objective To study the passive immunization with human monoclonal antibodies as for prophylaxis of human cytomegalovirus (HCMV) infection. Methods Fab monoclonal antibodies to HCMV were recovered by repertoire cloning of mRNA from a HCMV infected individual. Antigen binding specificity, CDR sequence of VH and VL and neutralizing activity on HCMV AD169 stain were analyzed in vitro. The light and heavy chain Fd fragment genes of Fab antibodies were further cloned into a recombinant baculovirus expression vector pAC-K-Fc to express intact IgG. Secreted products were purified with affinity chromatography using protein G. Results SDS-PAGE and Western blot confirmed the expression of the intact IgG. Immuno-blotting and -precipitation were used to identify HCMV proteins. One Fab monoclonal antibody recognized a conformational HCMV protein. Conclusion IgG antibodies can neutralize the HCMV AD169 strain efficiently at a titer of 2.5 μg/mL and may prove valuable for passive immunoprophylaxis against HCMV infection in humans. 展开更多
关键词 Human cytomegalovirus Human engineering antibody Phage display Recombinant baculovirus expression
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Human IgG1 C_γ1 Domain Is Crucial for the Bioactivity of the Engineered Anti-CD20 Antibodies 被引量:1
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作者 Shusheng Geng Jiannan Feng +6 位作者 Yan Li Xianjiang Kang Yingxun Sun Xin Gu Ying Huang Hong Chang Beifen Shen 《Cellular & Molecular Immunology》 SCIE CAS CSCD 2007年第2期121-125,共5页
In this study, we discussed the necessity of human IgG1 Cγ1 domain for recombinant antibody using computeraided homology modeling method and experimental studies. The heavy (VH) and light (VL) chain variable regi... In this study, we discussed the necessity of human IgG1 Cγ1 domain for recombinant antibody using computeraided homology modeling method and experimental studies. The heavy (VH) and light (VL) chain variable regions of 1-28, a murine IgM-type anti-CD20 mAb, were ligated by linker peptide (Gly4Ser)3 to form the single-chain Fv fragment (scFv). Then, the engineered antibody (LH1-3) was generated by fusing scFv with the entire IgG1 heavy constant regions. The 3-D structure of LH1-3 was modeled using computer-aided homology modeling method and the binding activity of LH1-3 was evaluated theoretically. Compared to the 3-D structure of the Fv fragment of the parent antibody, the conformation of the active pocket of LH1-3 was remained because of the rigid support of Cγ1. Further experimental results of flow cytometry showed that the engineered anti-CD20 antibody possessed specifically binding activity to CD20-expressing target cells. The anti-CD20 antibody fragments could also mediate complement-dependent cytotoxicity (CDC) of human B-lymphoid cell lines. Our study highlights some interests and advantages of a methodology based on the homology modeling and analysis of molecular structural properties. 展开更多
关键词 CD20 engineered antibody binding activity molecular modeling
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Antibody variable region engineering for improving cancer immunotherapy 被引量:6
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作者 Hantao Lou Xuetao Cao 《Cancer Communications》 SCIE 2022年第9期804-827,共24页
The efficacy and specificity of conventional monoclonal antibody(mAb)drugs in the clinic require further improvement.Currently,the development and application of novel antibody formats for improving cancer immunothera... The efficacy and specificity of conventional monoclonal antibody(mAb)drugs in the clinic require further improvement.Currently,the development and application of novel antibody formats for improving cancer immunotherapy have attracted much attention.Variable region-retaining antibody fragments,such as antigen-binding fragment(Fab),single-chain variable fragment(scFv),bispecific antibody,and bi/trispecific cell engagers,are engineered with humanization,multivalent antibody construction,affinity optimization and antibody masking for targeting tumor cells and killer cells to improve antibody-based therapy potency,efficacy and specificity.In this review,we summarize the application of antibody variable region engineering and discuss the future direction of antibody engineering for improving cancer therapies. 展开更多
关键词 antibody engineering bi/trispecific killer engager cancer immunotherapy chimeric antigen receptor-T(CAR-T)cell NANOBODY natural killer(NK)cell SCFV
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Streamlined human antibody generation and optimization by exploiting designed immunoglobulin loci in a B cell line
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作者 Hidetaka Seo Hitomi Masuda +15 位作者 Kenjiro Asagoshi Tomoaki Uchiki Shigehisa Kawata Goh Sasaki Takashi Yabuki Shunsuke Miyai Naoki Takahashi Shu-ichi Hashimoto Atsushi Sawada Aki Takaiwa Chika Koyama Kanako Tamai Kohei Kurosawa Ke-Yi Lin Kunihiro Ohta Yukoh Nakazaki 《Cellular & Molecular Immunology》 SCIE CAS CSCD 2021年第6期1545-1561,共17页
Monoclonal antibodies(mAbs)are widely utilized as therapeutic drugs for various diseases,such as cancer,autoimmune diseases,and infectious diseases.Using the avian-derived B cell line DT40,we previously developed an a... Monoclonal antibodies(mAbs)are widely utilized as therapeutic drugs for various diseases,such as cancer,autoimmune diseases,and infectious diseases.Using the avian-derived B cell line DT40,we previously developed an antibody display technology,namely,the ADLib system,which rapidly generates antigen-specific mAbs.Here,we report the development of a human version of the ADLib system and showcase the streamlined generation and optimization of functional human mAbs.Tailored libraries were first constructed by replacing endogenous immunoglobulin genes with designed human counterparts.From these libraries,clones producing full-length human IgGs against distinct antigens can be isolated,as exemplified by the selection of antagonistic mAbs.Taking advantage of avian biology,effective affinity maturation was achieved in a straightforward manner by seamless diversification of the parental clones into secondary libraries followed by single-cell sorting,quickly affording mAbs with improved affinities and functionalities.Collectively,we demonstrate that the human ADLib system could serve as an integrative platform with unique diversity for rapid de novo generation and optimization of therapeutic or diagnostic antibody leads.Furthermore,our results suggest that libraries can be constructed by introducing exogenous genes into DT40 cells,indicating that the ADLib system has the potential to be applied for the rapid and effective directed evolution and optimization of proteins in various fields beyond biomedicine. 展开更多
关键词 Immunoglobulin rearrangements homologous recombination antibody therapeutics antibody engineering drug discovery
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Protein engineering for natural product biosynthesis:expanding diversity for therapeutic applications
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作者 Sarah Oluwatobi Otun Jordy Alexis Lerma-Escalera +1 位作者 Khayalethu Ntushelo Ikechukwu Achilonu 《Journal of Bio-X Research》 2023年第2期49-60,共12页
In this dispensation of the fourth industrial revolution,protein engineering has become a popular approach for increasing enzymatic activity,stability,and titer in the biosynthesis of natural products.This is attribut... In this dispensation of the fourth industrial revolution,protein engineering has become a popular approach for increasing enzymatic activity,stability,and titer in the biosynthesis of natural products.This is attributed to its numerous advantages(over direct isolation from plants or via chemical synthesis),including decreasing or eliminating reaction byproducts,high precision,moderate handling of intricate and chemically unstable chemicals,overall reusability,and cost efficiency.Recently,protein engineering tools have advanced to redesign and enhance natural product biosynthesis.These methods include direct evolution,substrate engineering,medium engineering,enzyme engineering and immobilization,structure-assisted protein engineering,and advanced computational.Recent successes in implementing these emerging protein engineering technologies were critically discussed in this article.Also,the advantages,limitations,and applications in industrial and medical biotechnology were discussed.Last,future research directions and potential were also highlighted. 展开更多
关键词 antibodies engineering industrial enzymes natural product biosynthesis protein engineering POLYKETIDES synthetic biology
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Synthetic immunity to break down the bottleneck of cancer immunotherapy 被引量:2
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作者 陈志英 马飞 +1 位作者 黄海亮 何成宜 《Science Bulletin》 SCIE EI CAS CSCD 2015年第11期977-985,I0007,共10页
As a result of recent breakthroughs in cancer immunotherapies, unprecedented and durable remission, and even cure, has been reported in some patients. Importantly, this progress has been achieved, not by the induction... As a result of recent breakthroughs in cancer immunotherapies, unprecedented and durable remission, and even cure, has been reported in some patients. Importantly, this progress has been achieved, not by the induction of immunity, but by the delivery of immunity in the form of engineered antibodies (cAbs) or effector T cells. However, these single-target technologies have failed to result in a therapeutic effect in some patients, and evidence suggests that further advances depend on an effective strategy for coping with cancer heterogeneity and dynamics. A synthetic immunity (SI) strategy is proposed to achieve this goal. The fundamental basis of SI involves the generation of a panel of cAbs and antibody-retargeted CTLs designed to destroy all cell lineages of a cancer with high specificity. This goal can be achieved only when the composition of the cAbs is determined using a systematic approach, i.e., selecting the antigens targeted by the cAbs based on an epitope-tree illustrating the clonal antigen architecture of the cancer. Integration of technologies that increase the epitope breadth, cAb affinity and T cell activity will further enhance the efficacy of SI. Using DNA vectors to express the eAbs will be a safe, effective and affordable solution. 展开更多
关键词 Cancer immunotherapy Synthetic immunity Non-viral vector engineered antibody Bispecific antibody Retargeting T cell
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Current progress in innovative engineerec antibodies 被引量:11
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作者 William R. Strohl 《Protein & Cell》 SCIE CAS CSCD 2018年第1期86-120,共35页
As of May 1, 2017, 74 antibody-based molecules have been approved by a regulatory authority in a major market. Additionally, there are 70 and 575 antibody- based molecules in phase III and phase 1/11 clinical trials, ... As of May 1, 2017, 74 antibody-based molecules have been approved by a regulatory authority in a major market. Additionally, there are 70 and 575 antibody- based molecules in phase III and phase 1/11 clinical trials, respectively. These total 719 antibody-based clinical stage molecules include 493 naked IgGs, 87 antibody- drug conjugates, 61 bispecific antibodies, 37 total Fc fusion proteins, 17 radioimmunoglobulins, 13 antibody fragments, and 11 immunocytokines. New uses for these antibodies are being discovered each year. For oncol- ogy, many of the exciting new approaches involve anti- body modulation of T-cells. There are over 80 antibodies in clinical trials targeting T cell checkpoints, 26 T-cell- redirected bispecific antibodies, and 145 chimeric anti- gen receptor (CAR) cell-based candidates (all currently in phase I or II clinical trials), totaling more than 250 T cell interacting clinical stage antibody-based candi- dates. Finally, significant progress has been made recently on routes of delivery, including delivery of proteins across the blood-brain barrier, oral delivery to the gut, delivery to the cellular cytosol, and gene- and viral-based delivery of antibodies. Thus, there are cur- rently at least 864 antibody-based clinical stage mole- cules or cells, with incredible diversity in how they are constructed and what activities they impart. These are followed by a next wave of novel molecules, approa- ches, and new methods and routes of delivery, demon- strating that the field of antibody-based biologics is very innovative and diverse in its approaches to fulfill their promise to treat unmet medical needs. 展开更多
关键词 antibody clinical candidates engineered antibodies chimeric antigen receptors
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