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New therapeutic vaccination strategies for the treatment of chronic hepatitis B 被引量:9
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作者 Jia Liu Anna Kosinska +1 位作者 Mengji Lu Michael Roggendorf 《Virologica Sinica》 SCIE CAS CSCD 2014年第1期10-16,共7页
Chronic hepatitis B virus(CHB) is currently treated with either interferon-based or nucleot(s)idebased antiviral therapies.However,treatment with pegylated interferon alpha results in a durable antiviral response in o... Chronic hepatitis B virus(CHB) is currently treated with either interferon-based or nucleot(s)idebased antiviral therapies.However,treatment with pegylated interferon alpha results in a durable antiviral response in only about 30%patients and is associated with side effects.Most patients receiving nucleot(s)ide analogue treatment do not establish long-term,durable control of Infection and have rebounding viremia after cessation of therapy.Thus,novel therapy strategies are necessary to achieve the induction of potent and durable antiviral immune responses of the patients which can maintain long-term control of viral replication.Therapeutic vaccination of HBV carriers is a promising strategy for the control of hepatitis B.Here the authors review new therapeutic vaccination strategies to treat chronic hepatitis B which may be introduced for patient treatment in the future. 展开更多
关键词 hepatitis B virus woodchuck hepatitis virus therapeutic vaccination IMMUNOMODULATION programmed death-1
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An Overview of Quality Management of Therapeutic Vaccines in Clinical Trials in China
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作者 Lin Hansen Tian Lijuan 《Asian Journal of Social Pharmacy》 2024年第1期50-57,共8页
Objective To provide suggestions and a reference for improving the quality management system of clinical trials of therapeutic vaccines and promoting the development of therapeutic vaccines in China.Methods Literature... Objective To provide suggestions and a reference for improving the quality management system of clinical trials of therapeutic vaccines and promoting the development of therapeutic vaccines in China.Methods Literature research,case study and comparative study were used to analyze the quality management system of clinical trials of therapeutic vaccines.Results and Conclusion From the perspective of the sponsor,investigators and the thirdparty technical service company,the problems such as the low efficiency of clinical trial sample preparation and the lax implementation of the protocol by hospital departments in the quality management of clinical trials of therapeutic vaccines in China were found.Then,the optimization plan for the quality management of clinical trials of therapeutic vaccines is proposed,including optimizing the preparation process of therapeutic vaccines and strengthening the training of hospital department personnel. 展开更多
关键词 therapeutic vaccine clinical trial quality management good clinical practice(GCP)
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Development of therapeutic cancer vaccines using nanomicellar preparations 被引量:1
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作者 Yan Qin Wen-Feng Zeng Wei Liang 《Oncology and Translational Medicine》 2023年第6期265-268,共4页
Cancer treatment is a multifaceted challenge,and therapeutic vaccines have emerged as a promising approach.The micellar preparation efficiently encapsulates antigen polypeptides and enhances antigen presentation throu... Cancer treatment is a multifaceted challenge,and therapeutic vaccines have emerged as a promising approach.The micellar preparation efficiently encapsulates antigen polypeptides and enhances antigen presentation through the major histocompatibility class I pathway,promoting cytotoxic T lymphocyte immune responses.Moreover,it enables codelivery of both antigen and adjuvant to the same target antigen-presenting cells.Combining themicellar vaccine with traditional cancer treatments(such as chemotherapy,radiotherapy,and surgery)has demonstrated improved efficacy in murine tumor models.Overall,the polyethylene glycol-phosphatidylethanolamine micelle-based vaccine presents a promising platformfor cancer therapeutic vaccines.By leveraging the strengths of various treatmentmodalities,this innovative vaccine approach holds the potential to revolutionize cancer therapy and bring new possibilities for cancer patients. 展开更多
关键词 Intracellular codelivery Lymph node targeting PEG-PE micelle therapeutic cancer vaccine
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Toward a new era of hepatitis B virus therapeutics:The pursuit of a functional cure 被引量:12
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作者 Efthymios P Tsounis Evanthia Tourkochristou +1 位作者 Athanasia Mouzaki Christos Triantos 《World Journal of Gastroenterology》 SCIE CAS 2021年第21期2727-2757,共31页
Hepatitis B virus(HBV)infection,although preventable by vaccination,remains a global health problem and a major cause of chronic liver disease.Although current treatment strategies suppress viral replication very effi... Hepatitis B virus(HBV)infection,although preventable by vaccination,remains a global health problem and a major cause of chronic liver disease.Although current treatment strategies suppress viral replication very efficiently,the optimal endpoint of hepatitis B surface antigen(HBsAg)clearance is rarely achieved.Moreover,the thorny problems of persistent chromatin-like covalently closed circular DNA and the presence of integrated HBV DNA in the host genome are ignored.Therefore,the scientific community has focused on developing innovative therapeutic approaches to achieve a functional cure of HBV,defined as undetectable HBV DNA and HBsAg loss over a limited treatment period.A deeper understanding of the HBV life cycle has led to the introduction of novel direct-acting antivirals that exert their function through multiple mechanisms,including inhibition of viral entry,transcriptional silencing,epigenetic manipulation,interference with capsid assembly,and disruption of HBsAg release.In parallel,another category of new drugs aims to restore dysregulated immune function in chronic hepatitis B accompanied by lethargic cellular and humoral responses.Stimulation of innate immunity by pattern-recognition receptor agonists leads to upregulation of antiviral cytokine expression and appears to contribute to HBV containment.Immune checkpoint inhibitors and adoptive transfer of genetically engineered T cells are breakthrough technologies currently being explored that may elicit potent HBV-specific T-cell responses.In addition,several clinical trials are attempting to clarify the role of therapeutic vaccination in this setting.Ultimately,it is increasingly recognized that elimination of HBV requires a treatment regimen based on a combination of multiple drugs.This review describes the rationale for progressive therapeutic interventions and discusses the latest findings in the field of HBV therapeutics. 展开更多
关键词 Chronic hepatitis B Functional cure Direct-acting antivirals Gene silencing Immunotherapy therapeutic vaccination
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Immunotherapy and therapeutic vaccines in prostate cancer: an update on current strategies and clinical implications 被引量:6
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作者 B Harpreet Singh James L Gulley 《Asian Journal of Andrology》 SCIE CAS CSCD 2014年第3期364-371,共8页
In recent years, immunotherapy has emerged as a viable and attractive strategy for the treatment of prostate cancer. While there are multiple ways to target the immune system, therapeutic cancer vaccines and immune ch... In recent years, immunotherapy has emerged as a viable and attractive strategy for the treatment of prostate cancer. While there are multiple ways to target the immune system, therapeutic cancer vaccines and immune checkpoint inhibitors have been most successful in late-stage clinical trials. The landmark Food and Drug Administration approval of sipuleuceI-T for asymptomatic or minimally symptomatic metastatic prostate cancer set the stage for ongoing phase III trials with the cancer vaccine PSA-TRICOM and the immune checkpoint inhibitor ipilimumab. A common feature of these immune-based therapies is the appearance of improved overall survival without short-term changes in disease progression. This class effect appears to be due to modulation of tumor growth rate kinetics, in which the activated immune system exerts constant immunologic pressure that slows net tumor growth. Emerging data suggest that the ideal population for clinical trials of cancer vaccines is patients with lower tumor volume and less aggressive disease. Combination strategies that combine immunotherapy with standard therapies have been shown to augment both immune response and clinical benefit. 展开更多
关键词 androgen deprivation IMMUNOTHERAPY prostate cancer therapeutic cancer vaccines
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HBsAg, HBcAg, and combined HBsAg/HBcAg-based therapeutic vaccines in treating chronic hepatitis B virus infection 被引量:5
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作者 Sheikh Mohammad Fazle Akbar Mamun Al-Mahtab +1 位作者 Mohammad Helal Uddin Md. Sakirul Islam Khan 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS 2013年第4期363-369,共7页
BACKGROUND: As the host immunity is diminished in patients with chronic hepatitis B (CHB), different approaches have been used to up-regulate their immune responses to produce therapeutic effects. But, cytokines, grow... BACKGROUND: As the host immunity is diminished in patients with chronic hepatitis B (CHB), different approaches have been used to up-regulate their immune responses to produce therapeutic effects. But, cytokines, growth factors and polyclonal immune modulators could not exhibit sufficient therapeutic effects in these patients. Immune therapy with HBV-related antigens (vaccine therapy) has been used in CHB patients. But there is a paucity of information about the design of HBV antigen-based immune therapy in these patients. DATA SOURCE: Preclinical and clinical studies on immune therapy with HBsAg-based vaccine, HBcAg and combination of HBsAg/HBcAg-based vaccines have been discussed. RESULTS: HBsAg-based prophylactic vaccine was used as an immune therapeutic agent in CHB patients; however, monotherapy with HBsAg-based immune therapy could not lead to sustained control of HBV replication and/or liver damages. HBsAg-based vaccine was used as a combination therapy with cytokines, growth factors, and antiviral drugs. HBsAg-based vaccine was also used for cell-based therapy. However, satisfactory therapeutic effects of HBsAg-based vaccine could not be documented in CHB patients. In the mean time, evidences have supported that HBcAg-specific immunity is endowed with antiviral and liver protecting capacities in CHB patients. Recent data concentrate on the clinical use of combined HBsAg- and HBcAg-based vaccines in CHB patients.CONCLUSION: Antigen-based immune therapy with HBV- related antigens may be an alternative method for the treatment of CHB patients but proper designs of antigens, types of adjuvants, dose of vaccinations, and routes of administration need further analyses for the development of an effective regimen of immune therapy against HBV. 展开更多
关键词 chronic hepatitis B HBsAg vaccine HBsAg/HBcAg vaccine immune therapy therapeutic vaccines
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Activation and dramatically increased cytolytic activity of tumor specific T lymphocytes after radio-frequency ablation in patients with hepatocellular carcinoma and colorectal liver metastases 被引量:22
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作者 Johannes Hansler Thaddaus Till Wissniowski +4 位作者 Detlef Schuppan Astrid Witte Thomas Bernatik Eckhart Georg Hahn Deike Strobel 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第23期3716-3721,共6页
AIM: To assess if a specific cytotoxic T cell response can be induced in patients with malignant liver tumors treated with radio-frequency ablation (RFA). METHODS: Six Patients with liver metastases of colorectal ... AIM: To assess if a specific cytotoxic T cell response can be induced in patients with malignant liver tumors treated with radio-frequency ablation (RFA). METHODS: Six Patients with liver metastases of colorectal cancer and 6 with hepatocellular carcinoma (HCC) underwent RFA. Blood was sampled before, 4 and 8 wk after RFA. Test antigens were autologous liver and tumor lysate obtained from each patient by biopsy. Peripheral T cell activation was assessed by an interferon gamma (IFNγ) secretion assay and flow cytometry. T cells were double-stained for CD4/CD8 and IFNγ to detect cytotoxic T cells. The ratio of IFNγ positive and IFNγ negative T cells was determined as the stimulation index (SI). To assess cytolytic activity, T cells were co-incubated with human CaCo colorectal cancer and HepG2 HCC cells and release of cytosolic adenylate kinase was measured by a luciferase assay. RESULTS: Before RFA SI was 0.021 (±0.006) for CD4^+ and 0.022 (± 0.004) for CD8^+T cells against nonmalignant liver tissue and 0.018 (± 0.005) for CD4^+ and 0.021 (± 0.004) for CD8^+ cells against autologous tumor tissue. Four weeks after RFA SI against tumor tissue increased to 0.109 (± 0.005) for CD4+ and 0.11 (± 0.012) for CD8+ T cells against HCC, and to 0.115 (± 0.031) for CD4^+ and 0.15 (± 0.02) for CD8^+ cells for colorectal metastases (P 〈 0.0001). No increased SI was observed with nonmalignant tumor tissue at all time points. Before RFA cytolytic activity against the respect(ve cancer cells was low with 2.62 (± 0.37) relative luminescence units (RLU), but rose more than 100 fold 4 and 8 wk after RFA. Spontaneous release was 〈 2% of maximum release in all experiments. CONCLUSION: Patients with primary and secondary tumors of the liver show a significant tumor-specific cytotoxic T-cell stimulation with a dramatically increased tumor specific cytolytic activity of CD8^+ T cells after RFA. 展开更多
关键词 CD4 CD8 CYTOTOXIC Immune response IMMUNOLOGY IMMUNOTHERAPY Interferon gamma T cells NK therapeutic vaccination
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Nucleic acid vaccines: A taboo broken and prospect for a hepatitis B virus cure 被引量:3
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作者 Efthymios P Tsounis Athanasia Mouzaki Christos Triantos 《World Journal of Gastroenterology》 SCIE CAS 2021年第41期7005-7013,共9页
Although a prophylactic vaccine is available,hepatitis B virus(HBV)remains a major cause of liver-related morbidity and mortality.Current treatment options are improving clinical outcomes in chronic hepatitis B;howeve... Although a prophylactic vaccine is available,hepatitis B virus(HBV)remains a major cause of liver-related morbidity and mortality.Current treatment options are improving clinical outcomes in chronic hepatitis B;however,true functional cure is currently the exception rather than the rule.Nucleic acid vaccines are among the emerging immunotherapies that aim to restore weakened immune function in chronically infected hosts.DNA vaccines in particular have shown promising results in vivo by reducing viral replication,breaking immune tolerance in a sustained manner,or even decimating the intranuclear covalently closed circular DNA reservoir,the hallmark of HBV treatment.Although DNA vaccines encoding surface antigens administered by conventional injection elicit HBVspecific T cell responses in humans,initial clinical trials failed to demonstrate additional therapeutic benefit when administered with nucleos(t)ide analogs.In an attempt to improve vaccine immunogenicity,several techniques have been used,including codon/promoter optimization,coadministration of cytokine adjuvants,plasmids engineered to express multiple HBV epitopes,or combinations with other immunomodulators.DNA vaccine delivery by electroporation is among the most efficient strategies to enhance the production of plasmid-derived antigens to stimulate a potent cellular and humoral anti-HBV response.Preliminary results suggest that DNA vaccination via electroporation efficiently invigorates both arms of adaptive immunity and suppresses serum HBV DNA.In contrast,the study of mRNA-based vaccines is limited to a few in vitro experiments in this area.Further studies are needed to clarify the prospects of nucleic acid vaccines for HBV cure. 展开更多
关键词 Chronic hepatitis B therapeutic vaccination Nucleic acid vaccines DNA vaccines ELECTROPORATION IMMUNOTHERAPY
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Development of hepatitis C virus vaccine using hepatitis B core antigen as immuno-carrier 被引量:3
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作者 Jia-Yu Chen Fan Li 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第48期7774-7778,共5页
AIM: To develop hepatitis C virus (HCV) vaccine using HBcAg as the immuno-carrier to express HCV T epitope and to investigate its immunogenicity in mice. METHODS: We constructed the plasmid pTrc-coreNheI using gene en... AIM: To develop hepatitis C virus (HCV) vaccine using HBcAg as the immuno-carrier to express HCV T epitope and to investigate its immunogenicity in mice. METHODS: We constructed the plasmid pTrc-coreNheI using gene engineering technique, constructed the pcDNA3.1-coreNheI-GFP plasmid with GFP as the reporter gene, and transfected them into Hela cells. The expression of GFP was observed under confocal microscopy and the feasibility of using HBcAg as an immuno-carrier vaccine was studied. pTrc-core gene with a synthetic T epitope antigen gene of HCV (35-44aa) was fused and expressed in the plasmid pTrc- core-HCV (T). For the fusion of the HBcAg-T protein, sucrose, density gradient centrifugation was used, and its molecular weight and purity were analyzed by SDS- PAGE. Then balb/c mice were immunized by the plasmid with the HBcAg (expressed by pTrc-core) protein as control. The tumor regression potential was investigated in mice and evaluated at appropriate time. After three times of immunization, the peripheral blood and spleen of vaccinated mice were collected. HBcAb was detected by ELISA, and nonspecific T lymphocyte proliferation and response of splenocytes were respectively examined by MTT assay. T cell subset of blood and spleen were detected by FACS. RESULTS: GFP was successfully expressed. Tumor regression trial showed that no tumor formation was found in the group receiving immunization, while tumor xenograft progression was not changed in the control group. Strong nonspecific lymphocyte proliferation response was induced. FACS also showed that the ratio of CD8+ T cells in the experimental group was higher than the controls, but the serum HBcAb in experimental group was similar to the control. CONCLUSION: HBcAg can be used as an immuno-carrier of vaccine, the fusion of HBcAg-T protein could induce stronger cellular immune responses and it might be a candidate for therapeutic vaccines specific for HCV. 展开更多
关键词 Hepatitis C virus therapeutic vaccine T epitope Cellular immune responses
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Construction and characterization of calreticulin-HBsAg fusion gene recombinant adenovirus expression vector 被引量:1
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作者 Ma, Chun-Ling Wang, Gui-Bin +1 位作者 Gu, Run-Guo Wang, Fang 《World Journal of Gastroenterology》 SCIE CAS CSCD 2010年第24期3078-3082,共5页
AIM: To generate recombinant adenoviral vector con-taining calreticulin (CRT)-hepatitis B surface antigen (HBsAg) fusion gene for developing a safe, effective and HBsAg-specific therapeutic vaccine.METHODS: CRT and HB... AIM: To generate recombinant adenoviral vector con-taining calreticulin (CRT)-hepatitis B surface antigen (HBsAg) fusion gene for developing a safe, effective and HBsAg-specific therapeutic vaccine.METHODS: CRT and HBsAg gene were fused using polymerase chain reaction (PCR), endonuclease diges-tion and ligation methods. The fusion gene was cloned into pENTR/D-TOPO transfer vector after the base pairs of DNA (CACC) sequence was added to the 5′ end. Adenoviral expression vector containing CRT-HBsAg fusion gene was constructed by homologous recombinan-tion. The human embryo kidney (HEK) 293A cells were transfected with linearized DNA plasmid of the recombi-nant adenoviral vector to package and amplify recombi-nant adenovirus. The recombinant adenovirus titer was characterized using the end-dilution assay. The expres-sion of the CRT/HBsAg fusion protein in Ad-CRT/HBsAg infected 293A cells was detected by Western blotting.RESULTS: The CRT-HBsAg fusion gene was char-acterized by PCR and sequencing and its length and sequence were confirmed to be accurate. The CRT-HB-sAg fusion gene recombinant pENTR/D-TOPO transfer vector was constructed. The recombinant adenoviral vector, Ad-CRT/HBsAg, was generated successfully. The titer of Ad-CRT/HBsAg was characterized as 3.9 × 1011 pfu/mL. The CRT-HBsAg fusion protein was ex-pressed by HEK 293A cells correctly. CONCLUSION: CRT/HBsAg fusion gene recombinant replication-defective adenovirus expression vector is constructed successfully and this study has provided an experimental basis for further studies of Hepatitis B vi-rus gene therapy. 展开更多
关键词 CALRETICULIN Hepatitis B virus Hepatitis B surface antigen Adenovirus expression vector Fusion protein therapeutic vaccine
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Construction and evaluation of anti-gastrin immunogen based on P64K protein 被引量:1
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作者 Xiang-Hua Xiong Hong-Liang Zhao Chong Xue Wei Zhang Bing-Fen Yang Xue-Qin Yao Zhi-Min Liu 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第13期2040-2046,共7页
AIM: To construct two kinds of anti-gastrin immunogen based on P64K protein from Neisseria rneningitids and to compare their immunogenic effect. METHODS: G17P64K gene was cloned and ligated into pET28a plasmid, then... AIM: To construct two kinds of anti-gastrin immunogen based on P64K protein from Neisseria rneningitids and to compare their immunogenic effect. METHODS: G17P64K gene was cloned and ligated into pET28a plasmid, then transformed into BL21(DE3). After inoculation of LB medium and IPTG induction, the recombinant protein was solubly expressed at a high level. The purification of G17P64K fusion protein was similar to that of P64K. An initial step of purification consisting of 30% saturated ammonium sulfate precipitation was done, Additional fine optimizations included phenyl-sepharose, G200 Sephadex gel filtration and Q-sepharose anion exchanger chromatography. Highly purified protein was obtained and sequenced at the N-terminal amino acid residues. Polypeptide was synthesized by Fmoc solid phase chemical method and cross-linked to carrier protein P64K and DT mutant by MBS method and then the rabbit anti-gastrin 17 antibody was prepared by immunizing rabbit with cross-linked and fused protein. The titer and the activity in vitro of antibody were assessed. RESULTS: G17P64K gene and the recombinant bacteria were obtained. After four steps purification, protein sample that has the purity above 90% was achieved. At the 84^th day after the first immunization, the titer of antibody against cross-linked protein reached 51 200. Evaluation of the antibody in vitro manifested that it had a high inhibitory activity on the growth of tumor cell SW480. CONCLUSION: The P64K-polypeptide cross-linked immunogen immunized rabbit and achieved a higher titer antibody against gastrin 17 than the G17P64K fusion protein immunogen, which could inhibit the growth of the tumor cell SW480. 展开更多
关键词 GASTRIN P64K protein therapeutic vaccine
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Current progress in the development of prophylactic and therapeutic vaccines 被引量:4
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作者 Tingting Li Ciying Qian +3 位作者 Ying Gu Jun Zhang Shaowei Li Ningshao Xia 《Science China(Life Sciences)》 SCIE CAS CSCD 2023年第4期679-710,共32页
Vaccines are essential public health tools and play an important role in reducing the burden of infectious diseases in the population.Emerging infectious diseases and outbreaks pose new challenges for vaccine developm... Vaccines are essential public health tools and play an important role in reducing the burden of infectious diseases in the population.Emerging infectious diseases and outbreaks pose new challenges for vaccine development,requiring the rapid design and production of safe and effective vaccines against diseases with limited resources.Here,we focus on the development of vaccines in broad fields ranging from conventional prophylactic vaccines against infectious diseases to therapeutic vaccines against chronic diseases and cancer,providing a comprehensive overview of recent advances in eight different vaccine forms(live attenuated vaccines,inactivated vaccines,polysaccharide and polysaccharide conjugate vaccines,recombinant subunit vaccines,virus-like particle and nanoparticle vaccines,polypeptide vaccines,DNA vaccines,and m RNA vaccines)and the therapeutic vaccines against five solid tumors(lung cancer,breast cancer,colorectal cancer,liver cancer and gastric cancer),three infectious diseases(human immunodeficiency virus,hepatitis B virus and human papillomavirus-induced diseases)and three common chronic diseases(hypertension,diabetes mellitus and dyslipidemia).We aim to provide new insights into vaccine technologies,platforms,applications and understanding of potential next-generation preventive and therapeutic vaccine technologies,paving the way for the vaccines design in the future. 展开更多
关键词 prophylactic vaccine therapeutic vaccine immune response infectious diseases CANCERS chronic diseases
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Construction of Recombinant Modified Vaccinia Ankara(MVA) Expressing Hepatitis B Virus Surface Antigen
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作者 CHEN Yu YANG Xiao-song YU Xiang-hui JIANG Chun-lai WU Yong-ge JIN Ying-hua CHEN Yue CHEN Yan LI Wei KONG Wei 《Chemical Research in Chinese Universities》 SCIE CAS CSCD 2006年第2期213-216,共4页
The T lymphocyte response has been shown to be the determinant in the clearance of many viral infections. Hence, therapeutic vaccine candidates against HBV are designed to enhance this response of the immune system. V... The T lymphocyte response has been shown to be the determinant in the clearance of many viral infections. Hence, therapeutic vaccine candidates against HBV are designed to enhance this response of the immune system. Vaccinia virus vector-based vaccines have been proposed as excellent candidates to elicit long-term and strong T lymphocyte mediated immune responses. In this study, the recombinant MVA expressing HBV surface antigen has been constructed, which can elicit a potent T cell mediated response. The ELISA results for the surface protein in the medium of the recombinant MVA, strongly indicate that the recombinant virus has been successfully obtained. 展开更多
关键词 Recombinant MVA therapeutic vaccine T lymphocyte response
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Bidirectional crosstalk between therapeutic cancer vaccines and the tumor microenvironment:Beyond tumor antigens
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作者 Si-Wei Zhang Han Wang +5 位作者 Xiao-Hong Ding Yu-Ling Xiao Zhi-Ming Shao Chao You Ya-Jia Gu Yi-Zhou Jiang 《Fundamental Research》 CSCD 2023年第6期1005-1024,共20页
Immunotherapy has rejuvenated cancer therapy,especially after anti-PD-(L)1 came onto the scene.Among the many therapeutic options,therapeutic cancer vaccines are one of the most essential players.Although great progre... Immunotherapy has rejuvenated cancer therapy,especially after anti-PD-(L)1 came onto the scene.Among the many therapeutic options,therapeutic cancer vaccines are one of the most essential players.Although great progress has been made in research on tumor antigen vaccines,few phase III trials have shown clinical benefits.One of the reasons lies in obstruction from the tumor microenvironment(TME).Meanwhile,the therapeutic cancer vaccine reshapes the TME in an ambivalent way,leading to immune stimulation or immune escape.In this review,we summarize recent progress on the interaction between therapeutic cancer vaccines and the TME.With respect to vaccine resistance,innate immunosuppressive TME components and acquired resistance caused by vaccination are both involved.Understanding the underlying mechanism of this crosstalk provides insight into the treatment of cancer by directly targeting the TME or synergizing with other therapeutics. 展开更多
关键词 therapeutic cancer vaccine Tumor microenvironment Acquired resistance Immunosupportive IMMUNOSUPPRESSIVE
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A citrullinated antigenic vaccine in treatment of autoimmune arthritis
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作者 Xu Jin Tianya Dong +14 位作者 Qian Wang Yang Xie Xiangyu Fang Chaonan Wei Shuyan Liu Xi Zheng Ping Wang Danxue Zhu Lulu Cao Suwei Dong Kechi Fang Chao Zhong Jing Wang Fanlei Hu Zhanguo Li 《Science Bulletin》 SCIE EI CAS CSCD 2024年第18期2920-2929,共10页
Rheumatoid arthritis(RA)is an inflammatory autoimmune disease triggered by antigenic peptides with environmental and genetic risk factors.It has been shown that antigen-specific targeting could be a promising therapeu... Rheumatoid arthritis(RA)is an inflammatory autoimmune disease triggered by antigenic peptides with environmental and genetic risk factors.It has been shown that antigen-specific targeting could be a promising therapeutical strategy for RA by restoring immune tolerance to self-antigens without compromising normal immunity.Citrullination of antigens enhances antigenic properties and induces autoimmune responses.Here,we showed that citrullinated antigenic(citAg)vaccine ameliorated collageninduced arthritis with decreased T-helper 1(Th1)and Th17 cells,downregulated proinflammatory cytokines including interlukin-6 and tumor necrosis factor-a,and inhibited antigen recall responses.B cell receptor sequencing further revealed that citAg vaccine could dampen the dysregulated V(D)J recombination,restoring the immune repertoire.Taken together,the results demonstrated that citAg vaccine might have a therapeutic effect on RA. 展开更多
关键词 CitAg CITRULLINATION Collagen typeⅡ therapeutic vaccine Immune tolerance Rheumatoid arthritis
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Development of mRNA vaccines and their prophylactic and therapeutic applications 被引量:3
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作者 Kyuri Lee Minjeong Kim +1 位作者 Yunmi Seo Hyukjin Lee 《Nano Research》 SCIE EI CAS CSCD 2018年第10期5173-5192,共20页
Nucleic acid vaccines have attracted enormous attention for resolving the limitations of conventional vaccines using live attenuated viruses. Because nucleic acid vaccines can be produced rapidly in response to the em... Nucleic acid vaccines have attracted enormous attention for resolving the limitations of conventional vaccines using live attenuated viruses. Because nucleic acid vaccines can be produced rapidly in response to the emergence of new virus strains, they are more appropriate for the control of urgent epidemic and pandemic issues. In particular, messenger RNA (mRNA) vaccines have evolved as a new type of nucleic acid vaccines in accordance with their superior protein expression and a lack of mutagenesis as compared with DNA vaccines. Using mRNA vaccines, large amounts of target proteins can be expressed in immune cells for efficient immunization. For instance, antigen-specific vaccination is a feasible option involving the expression of specific antigens in antigen-presenting cells. Immunological reactions are modulated by expressing several proteins associated with stimulation or maturation of immune cells. In addition, mRNA vaccines can stimulate innate immunity through specific recognition by pattern recognition receptors. On the basis of these remarkable properties, mRNA vaccines have been used for prophylactic and therapeutic applications. This review highlights the role of mRNA vaccines as prophylactic vaccines for prevention of future infections and as therapeutic vaccines for cancer immunotherapy. In addition to the conventional type of mRNA vaccines, RNA replicons (self-amplifying mRNA vaccines) will be described. 展开更多
关键词 messenger RNA (mRNA) vaccines prophylactic vaccines self-amplifying mRNA vaccines therapeutic vaccine cancer immunotherapy
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Therapeutic dendritic cell vaccines engineered with antigen-biomineralized Bi_(2)S_(3) nanoparticles for personalized tumor radioimmunotherapy 被引量:1
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作者 Huan Yu Haoxiang Guo +5 位作者 He Zu Heng Ding Subin Lin Yangyun Wang Leshuai W Zhang Yong Wang 《Aggregate》 2022年第5期227-237,共11页
Therapeutic vaccines,an exciting development in cancer immunotherapy,share the goal of priming of personalized antigen-specific T-cell response by precise antigen presentation of dendritic cells(DCs),but major obstacl... Therapeutic vaccines,an exciting development in cancer immunotherapy,share the goal of priming of personalized antigen-specific T-cell response by precise antigen presentation of dendritic cells(DCs),but major obstacles include insufficient antigen loading and off-target to DCs remain to their success.Here,we developed an imageable therapeutic vaccine with whole-antigen loading and target delivery constructed by ovalbumin(OVA)-biomineralized Bi_(2)S_(3) nanoparticles-pulsed DCs.Relying on the strong X-ray absorption and fluorescence labeling performance of Bi_(2)S_(3)@OVA nanoparticles,the in vivo spatiotemporal fate of the vaccine(Bi_(2)S_(3)@OVA@DC)can be noninvasively monitored by computed tomography and near-infrared fluorescence imaging in real time.The Bi_(2)S_(3)@OVA@DC can rapidly and durably accumulate in draining lymph nodes and thus trigger stronger T-cell responses compared to OVA-pulsed DCs.Meanwhile,Bi_(2)S_(3)@OVA@DC can further achieve in vivo antitumor effects against OVA-expressing B16F10 melanoma when combined with fractionated radiotherapy,resulting from the upregulation of cytotoxic CD8^(+)T cells and restraint of regulatory T cells in the tumor microenvironment,and the systemical secretion of OVA-specific IgG1/IgG2α antibody.Overall,we successfully fabricated an engineered DC vaccine featured in high whole-antigen loading capacity that can be precisely delivered to the lymphatic system for visualization,serving as a powerful therapeutic platform for cancer radioimmunotherapy. 展开更多
关键词 antigen-biomineralized Bi_(2)S_(3)nanoparticles dendritic cells RADIOIMMUNOTHERAPY therapeutic vaccines visualization
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Overcoming HBV immune tolerance to eliminate HBsAg-positive hepatocytes via pre-administration of GM-CSF as a novel adjuvant for a hepatitis B vaccine in HBV transgenic mice 被引量:11
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作者 Xianzheng Wang Aihua Dong +5 位作者 Jingjing Xiao Xingjun Zhou Haili Mi Hanqian Xu Jiming Zhang Bin Wang 《Cellular & Molecular Immunology》 SCIE CAS CSCD 2016年第6期849-861,共13页
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to be a potential vaccine adjuvant despite contradictory results from animal and human studies. The discrepancies may be due to the different doses ... Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to be a potential vaccine adjuvant despite contradictory results from animal and human studies. The discrepancies may be due to the different doses and regimens of GM-CSF that were used, given that either mature or immature dendritic cells (DCs) could be induced under different conditions. To test the hypothesis that GM-CSF can be used as a novel adjuvant for a hepatitis B virus (HBV) therapeutic vaccine, we administered GM-CSF once per day for three days prior to vaccination with recombinant HBV vaccine (rHBVvac) in mice. We observed greater DC maturation in these pre-treated animals at day 3 as compared to day 1 or day 2 of daily GM-CSF administration. This strategy was further investigated for its ability to break the immune tolerance established in hepatitis B surface antigen-transgenic (HBsAg-Tg) animals. We found that the levels of induced anti-HBsAg antibodies were significantly higher in animals following three days of GM-CSF pre-treatment before rHBV vaccination after the third immunization. In addition to the increase in anti-HBsAg antibody levels, cell-mediated anti-HBsAg responses, including delayed-type hypersensitivity, T-cell proliferation, interferon-y production, and cytotoxic T lymphocytes, were dramatically enhanced in the three-day GM-CSF pre-treated group. After adoptive transfers of CD8+ T cells from immunized animals, antigen-specific CD8+ T cells were observed in the livers of recipient HBsAg-Tg animals. Moreover, the three-day pre-treatments with GM-CSF prior to rHBVvac vaccination could significantly eliminate HBsAg-positive hepatocytes, suggesting beneficial therapeutic effects. Therefore, this protocol utilizing GM-CSF as an adjuvant in combination with the rHBVvac vaccine has the potential to become a novel immunotherapy for chronic hepatitis B patients. 展开更多
关键词 ADJUVANT chronic hepatitis B GM-CSF immune-tolerance therapeutic vaccine
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Albumin fusion with granulocyte-macrophage colony-stimulating factor acts as an immunotherapy against chronic tuberculosis 被引量:6
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作者 Yu-Min Chuang Liangmei He +5 位作者 Michael L.Pinn Ya-Chea Tsai Max A.Cheng Emily Farmer Petros C.Karakousis Chien-Fu Hung 《Cellular & Molecular Immunology》 SCIE CAS CSCD 2021年第10期2393-2401,共9页
A long duration of treatment and emerging drug resistance pose significant challenges for global tuberculosis(TB)eradication efforts.Therefore,there is an urgent need to develop novel strategies to shorten TB treatmen... A long duration of treatment and emerging drug resistance pose significant challenges for global tuberculosis(TB)eradication efforts.Therefore,there is an urgent need to develop novel strategies to shorten TB treatment regimens and to treat drug-resistant TB.Using an albumin-fusion strategy,we created a novel albumin-fused granulocyte-macrophage colony-stimulating factor(albGM-CSF)molecule that harnesses albumin’s long half-life and targeting abilities to enhance the biostability of GM-CSF and direct it to the lymph nodes,where the effects of GM-CSF can increase dendritic cell populations crucial for eliciting a potent immune response.In this study,we demonstrate that albGM-CSF serves as a novel immunotherapy for chronic Mycobacterium tuberculosis(Mtb)infections by enhancing GM-CSF biostability in serum.Specifically,albumin is very safe,stable,and has a long half-life,thereby enhancing the biostability of GM-CSF.In the lungs and draining lymph nodes,albGM-CSF is able to increase the numbers of dendritic cells,which are crucial for the activation of naive T cells and for eliciting potent immune responses.Subcutaneous administration of albGM-CSF alone reduced the mean lung bacillary burden in mice with chronic tuberculosis infection.While GM-CSF administration was associated with IL-1βrelease from Mtb-infected dendritic cells and macrophages,higher IL-1βlevels were observed in albGM-CSF-treated mice with chronic tuberculosis infection than in mice receiving GM-CSF.Albumin fusion with GM-CSF represents a promising strategy for the control of chronic lung tuberculosis infections and serves as a novel therapeutic vaccination platform for other infectious diseases and malignancies. 展开更多
关键词 TUBERCULOSIS ALBUMIN GM-CSF therapeutic vaccine fusion protein
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Novel exosome-targeted T-cell-based vaccine counteracts T-cell anergy and converts CTL exhaustion in chronic infection via CD40L signaling through the mTORC1 pathway 被引量:5
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作者 Rong Wang Aizhang Xu +4 位作者 Xueying Zhang Jie Wu Andrew Freywald Jianqing Xu Jim Xiang 《Cellular & Molecular Immunology》 SCIE CAS CSCD 2017年第6期529-545,共17页
CD8+ cytotoxic T lymphocyte (CTL) exhaustion is a chief issue for ineffective virus elimination in chronic infectious diseases. We generated novel ovalbumin (OVA)-specific OVA-Texo and HIV-specific Gag-Texo vacci... CD8+ cytotoxic T lymphocyte (CTL) exhaustion is a chief issue for ineffective virus elimination in chronic infectious diseases. We generated novel ovalbumin (OVA)-specific OVA-Texo and HIV-specific Gag-Texo vaccines inducing therapeutic immunity. To assess their therapeutic effect in chronic infection, we developed a new chronic infection model by i.v. infecting C57BL/6 mice with the OVA-expressing adenovirus AdVova. During chronic AdVova infection, mouse CTLs were found to express the inhibitory molecules programmed cell-death protein-1 (PD-1) and lymphocyte-activation gene-3 (LAG-3) and to be functionally exhausted, showing a significant deficiency in T-cell proliferation, IFN-7 production and cytolytic effects. Naive CD8+ T cells upregulated inhibitory PD-ligand 1 (PD-L1), B- and T-lymphocyte attenuator and T-cell anergy-associated molecules (Grail and Itch) while down-regulating the proliferative response upon stimulation in mice with chronic infection. Remarkably, the OVA-Texo vaccine counteracted T-cell anergy and converted CTL exhaustion. The latter was associated with (i) the upregulation of a marker for CTL functionality, diacetylated histone-H3 (diAcH3), (ii) a fourfold increase in CTLs, occurring independent of host DCs or CD4+ T cells, and (iii) the restoration of CTL IFN-7 production and cytotoxicity. In vivo OVA-Texo-stimulated CTLs upregulated the activities of the mTORC1 pathway-related molecules Akt, S6, elF4E and T-bet, and treatment of the CTLs with an mTORC1 inhibitor, rapamycin, significantly reduced the OVA-Texo- induced increase in CTLs. Interestingly, OVA-Texo-mediated CD40L signaling played a critical role in the observed immunological effects. Importantly, the Gag-Texo vaccine induced Gag-specific therapeutic immunity in chronic infection. Therefore, this study should have a serious impact on the development of new therapeutic vaccines for human immunodeficiency virus (HIV-1) infection. 展开更多
关键词 anti-CD40 Ab CD40L signaling chronic infection CTL exhaustion HIV Gag mTORC1 pathway T-cellanergy therapeutic T-cell vaccine
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