Pancreatic cancer is characterized by inter-tumoral and intra-tumoral heterogeneity,especially in genetic alteration and microenvironment.Conventional therapeutic strategies for pancreatic cancer usually suffer resist...Pancreatic cancer is characterized by inter-tumoral and intra-tumoral heterogeneity,especially in genetic alteration and microenvironment.Conventional therapeutic strategies for pancreatic cancer usually suffer resistance,highlighting the necessity for personalized precise treatment.Cancer vaccines have become promising alternatives for pancreatic cancer treatment because of their multifaceted advantages including multiple targeting,minimal nonspecific effects,broad therapeutic window,low toxicity,and induction of persistent immunological memory.Multiple conventional vaccines based on the cells,microorganisms,exosomes,proteins,peptides,or DNA against pancreatic cancer have been developed;however,their overall efficacy remains unsatisfactory.Compared with these vaccine modalities,messager RNA(mRNA)-based vaccines offer technical and conceptional advances in personalized precise treatment,and thus represent a potentially cutting-edge option in novel therapeutic approaches for pancreatic cancer.This review summarizes the current progress on pancreatic cancer vaccines,highlights the superiority of mRNA vaccines over other conventional vaccines,and proposes the viable tactic for designing and applying personalized mRNA vaccines for the precise treatment of pancreatic cancer.展开更多
Cholangiocarcinoma(CHOL)is one of the most aggressive tumors worldwide and cannot be effectively treated by conventional and novel treatments,including immune checkpoint blockade therapy.The mRNA vaccine-based immunot...Cholangiocarcinoma(CHOL)is one of the most aggressive tumors worldwide and cannot be effectively treated by conventional and novel treatments,including immune checkpoint blockade therapy.The mRNA vaccine-based immunotherapeutic strategy has attracted much attention for various diseases,however,its application in CHOL is limited due to the thoughtlessness in the integration of vaccine design and patient selection.A recent study established an integrated path for identifying potent CHOL antigens for mRNA vaccine development and a precise stratification for identifying CHOL patients who can benefit from the mRNA vaccines.In spite of a promising prospect,further investigations should identify immunogenic antigens and onco-immunological characteristics of CHOL to guide the clinical application of CHOL mRNA vaccines in the future.展开更多
BACKGROUND mRNA vaccines have been investigated in multiple tumors,but limited studies have been conducted on their use for hepatocellular carcinoma(HCC).AIM To identify candidate mRNA vaccine antigens for HCC and sui...BACKGROUND mRNA vaccines have been investigated in multiple tumors,but limited studies have been conducted on their use for hepatocellular carcinoma(HCC).AIM To identify candidate mRNA vaccine antigens for HCC and suitable subpopu-lations for mRNA vaccination.METHODS Gene expression profiles and clinical information of HCC datasets were obtained from International Cancer Genome Consortium and The Cancer Genome Atlas.Genes with somatic mutations and copy number variations were identified by cBioPortal analysis.The differentially expressed genes with significant prognostic value were identified by Gene Expression Profiling Interactive Analysis 2 website analysis.The Tumor Immune Estimation Resource database was used to assess the correlation between candidate antigens and the abundance of antigen-presenting cells(APCs).Tumor-associated antigens were overexpressed in tumors and associated with prognosis,genomic alterations,and APC infiltration.A consensus cluster analysis was performed with the Consensus Cluster Plus package to identify the immune subtypes.The weighted gene coexpression network analysis(WGCNA)was used to determine the candidate biomarker molecules for appropriate populations for mRNA vaccines.immune subtypes showed distinct cellular and clinical characteristics.The IS1 and IS3 immune subtypes were immunologically“cold”.The IS2 and IS4 immune subtypes were immunologically“hot”,and the immune checkpoint genes and immunogenic cell death genes were upregulated in these subtypes.IS1-related modules were identified with the WGCNA algorithm.Ultimately,five hub genes(RBP4,KNG1,METTL7A,F12,and ABAT)were identified,and they might be potential biomarkers for mRNA vaccines.CONCLUSION AURKA,CCNB1,CDC25C,CDK1,TRIP13,PES1,MCM3,PPM1G,NEK2,KIF2C,PTTG1,KPNA2,and PRC1 have been identified as candidate HCC antigens for mRNA vaccine development.The IS1 and IS3 immune subtypes are suitable populations for mRNA vaccination.RBP4,KNG1,METTL7A,F12,and ABAT are potential biomarkers for mRNA vaccines.展开更多
BACKGROUND As of 31 December 2022,there were over 6.6 million coronavirus disease 2019(COVID-19)deaths and over 651 million cases across 200 countries worldwide.Despite the increase in vaccinations and booster shots,C...BACKGROUND As of 31 December 2022,there were over 6.6 million coronavirus disease 2019(COVID-19)deaths and over 651 million cases across 200 countries worldwide.Despite the increase in vaccinations and booster shots,COVID-19 cases and deaths continue to remain high.While the effectiveness of these vaccines has already been established by different manufacturers,the fact remains that these vaccines were created quickly for global emergency use,tested under controlled clinical conditions from voluntary subjects and age groups whose general characteristics may differ from the actual general population.AIM To conduct a systematic review to determine the real-world effectiveness of mRNA COVID-19 vaccines in the elderly during the predominance of Delta and Omicron variants in preventing COVID-19 related infection,hospital,intensive care unit(ICU)admission and intubation,and death.METHODS A combination of Medical Subject Headings and non–Medical Subject Headings was carried out to identify all relevant research articles that meets the inclusion and exclusion criteria from PubMed,Cochrane,CINAHL,Scopus,ProQuest,EMBASE,Web of Science,and Google Scholar databases,as well as qualified research studies from pre–print servers using medRxiv and Research Square,published from January 1,2021-December 31,2022.RESULTS As per the inclusion and exclusion criteria,the effectiveness of Pfizer-BioNTech and Moderna vaccines were evaluated from an estimated total study population of 26535692 using infection,hospital,ICU admission and intubation,and death as outcome measures from studies published between 2021 and 2022,conducted in New York,Finland,Canada,Costa Rica,Qatar,Greece,and Brazil.The risk of bias was evaluated using risk of bias in nonrandomized studies of interventions(ROBINS-I)tool for cohort,case-control,and cross-sectional studies.While clinical trial data on Pfizer-BioNTech and Moderna vaccines demonstrated 94%vaccine effectiveness in the elderly,the results in this study showed that vaccine effectiveness in real-world settings is marginally lower against infection(40%-89%),hospitalization(92%),ICU admission and intubation(98%-85%),and death(77%-87%)with an indication of diminished effectiveness of vaccine over time.Furthermore,2 doses of mRNA vaccines are inadequate and only provides interim protection.CONCLUSION Because of the natural diminishing effectiveness of the vaccine,the need for booster dose to restore its efficacy is vital.From a research perspective,the use of highly heterogeneous outcome measures inhibits the comparison,contrast,and integration of the results which makes data pooling across different studies problematic.While pharmaceutical intervention like vaccination is important to fight an epidemic,utilizing common outcome measurements or carrying out studies with minimal heterogeneity in outcome measurements,is equally crucial to better understand and respond to an international health crisis.展开更多
mRNA vaccines have emerged as promising alternative platforms to conventional vaccines.Their ease of production,low cost,safety profile and high potency render them ideal candidates for prevention and treatment of inf...mRNA vaccines have emerged as promising alternative platforms to conventional vaccines.Their ease of production,low cost,safety profile and high potency render them ideal candidates for prevention and treatment of infectious diseases,especially in the midst of pandemics.The challenges that face in vitro transcribed RNA were partially amended by addition of tethered adjuvants or co-delivery of naked mRNA with an adjuvanttethered RNA.However,it wasn’t until recently that the progress made in nanotechnology helped enhance mRNA stability and delivery by entrapment in novel delivery systems of which,lipid nanoparticles.The continuous advancement in the fields of nanotechnology and tissue engineering provided novel carriers for mRNA vaccines such as polymeric nanoparticles and scaffolds.Various studies have shown the advantages of adopting mRNA vaccines for viral diseases and cancer in animal and human studies.Self-amplifying mRNA is considered today the next generation of mRNA vaccines and current studies reveal promising outcomes.This review provides a comprehensive overview of mRNA vaccines used in past and present studies,and discusses future directions and challenges in advancing this vaccine platform to widespread clinical use.展开更多
For centuries,therapeutic cancer vaccines have been developed and tried clinically.Way back in the late 19th century,the Father of Immunotherapy,William Coley had discovered that bacterial toxins were effective for in...For centuries,therapeutic cancer vaccines have been developed and tried clinically.Way back in the late 19th century,the Father of Immunotherapy,William Coley had discovered that bacterial toxins were effective for inoperable sarcomas.In the 1970s,the Bacillus Calmette-Guérin(BCG)vaccine was repurposed,e.g.,for advanced melanomas.Then,therapeutic cancer vaccines based on tumorassociated antigens(found on the surfaces of cancer cells)were tried clinically but apparently have not made a really significant clinical impact.For repurposed pathogen vaccines,only the BCG vaccine was approved in 1989 for local application to treat nonmuscle-invading bladder cancers.Although the mildly toxic vaccine adjuvants deliberately added to conventional pathogen vaccines are appropriate for seasonal applications,when repurposed for continual oncology usage,toxicity may be problematic.In 2010,even with the approval of sipuleucel-T as the very first cancer vaccine(dendritic cell)developed for designated prostate cancers,it has also not made a really significant clinical impact.Perhaps more"user friendly"cancer vaccines should be explored.As from approximately 30 years ago,the safety and effectiveness of mRNA vaccination for oncology had already been studied,the current coronavirus disease 2019 pandemic,though disastrous,has given such progressively advancing technology a kickstart.For oncology,other virtues of mRNA vaccines seem advantageous,e.g.,rapid and versatile development,convenient modular design,and entirely cell-free synthesis,are being progressively recognized.Moreover,mRNAs encoding various oncology antigens for vaccination may also be tested with the combination of relatively non-toxic modalities of oncology treatments,e.g.,metformin or metronomic(low-dose,prolonged administration)chemotherapy.Admittedly,robust clinical data obtained through good quality clinical trials are mandatory.展开更多
BACKGROUND We present a rare case of status epilepticus in a 56-year-old man which arose as a complication after vaccination with the coronavirus disease 2019(COVID-19)mRNA-1273 vaccine.The patient's history inclu...BACKGROUND We present a rare case of status epilepticus in a 56-year-old man which arose as a complication after vaccination with the coronavirus disease 2019(COVID-19)mRNA-1273 vaccine.The patient's history included well-compensated secondary epilepsy.The root cause of the situation was a fever which had developed as a side effect of the vaccination.CASE SUMMARY A 56-year-old man received the first dose of mRNA-1273 vaccine against the severe acute respiratory syndrome-coronavirus-2.The vaccine was administered intramuscularly(100 mg,0.5 mL).The next morning the man was found to be suffering from fever and headaches while at the same time experiencing general weakness.He lost consciousness suddenly and experienced generalized clonic seizures which turned into status epilepticus.When the Emergency Medical Service arrived the patient was unconscious with spontaneous breathing and generalized clonic seizures.It was necessary to administer diazepam repeatedly.It was also necessary to administer high doses of levetiracetam and temporary propofol.The status epilepticus was brought under control approximately 90 min after the patient’s transport to the Emergency Department.A follow-up electroencephalogram no longer revealed abnormal indications of epileptic fit.The patient was temporarily hospitalized in the Intensive Care Unit and after seven days care was discharged without any further apparent effects.CONCLUSION There is currently no specific treatment against COVID-19.Therefore,the benefits of COVID-19 vaccine protection outweigh the risks.展开更多
BACKGROUND A 70-year-old man with hepatitis C virus-related recurrent hepatocellular carcinoma was admitted for further diagnosis of a 1 cm iso-hyperechoic nodule in segment(S)5.CASE SUMMARY Gadolinium ethoxybenzyl di...BACKGROUND A 70-year-old man with hepatitis C virus-related recurrent hepatocellular carcinoma was admitted for further diagnosis of a 1 cm iso-hyperechoic nodule in segment(S)5.CASE SUMMARY Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging(EOB-MRI)revealed the nodule in S5 with a defect at the hepatobiliary phase,hyperintensity on diffusion weighted imaging(DWI)and hypointensity on apparent diffusion coefficient(ADC)map.Contrast-enhanced computed tomography revealed hypervascularity at the early phase,and delayed contrast-enhancement was observed at the late phase.Contrast-enhanced ultrasound(US)revealed incomplete defect at the late vascular phase.Inflammatory liver tumor,lymphoproliferative disease,intrahepatic cholangiocarcinoma(small duct type)and bile duct adenoma were suspected through the imaging studies.US guided biopsy,however,showed a noncaseating hepatic sarcoid-like epithelioid granuloma(HSEG),and histopathological analysis disclosed spindle shaped epithelioid cells harboring Langhans-type multinucleated giant cells.One month after admission,EOB-MRI signaled the disappearance of the defect at the hepatobiliary phase,of hyperintensity on DWI,of hypointensity on ADC map,and no stain at the early phase.CONCLUSION That the patient had received BNT162b2 messenger RNA(mRNA)coronavirus disease 2019 vaccination 3 mo before the occurrence of HSEG,and that its disappearance was confirmed 4 mo after mRNA vaccination suggested that the drug-induced sarcoidosis-like reaction(DISR)might be induced by the mRNA vaccination.Fortunately,rechallenge of drug-induced DISR with the third mRNA vaccination was not confirmed.展开更多
目的构建通用流感mRNA疫苗并全面评价其免疫保护效果。方法优化流感病毒株A/California/04/2009的血凝素(hemagglutinin,HA)、核蛋白(nucleoprotein,NP)和基质蛋白2胞外区(matrix protein 2 ectodomain,M2e)抗原序列,并将HA、NP和3个串...目的构建通用流感mRNA疫苗并全面评价其免疫保护效果。方法优化流感病毒株A/California/04/2009的血凝素(hemagglutinin,HA)、核蛋白(nucleoprotein,NP)和基质蛋白2胞外区(matrix protein 2 ectodomain,M2e)抗原序列,并将HA、NP和3个串联的M2e(3M2e)分别克隆至pcDNA3.1载体,通过线性化、体外转录、酶学法加帽、酶促加尾合成mRNA,命名为mRNA-HA、mRNA-NP和mRNA-3M2e。3种mRNA分别转染293T细胞后,通过免疫荧光实验鉴定蛋白的表达。利用脂质纳米颗粒分别包裹mRNA-HA、mRNA-NP和mRNA-3M2e并测量其粒径和电位。再将3种mRNA等体积混合制备成Comb-mRNA疫苗。将28只6周雌性Balb/c小鼠(体质量为18~22 g)按简单随机分组法分为2组:LNP组(n=14)和Comb-mRNA组(n=14)。通过血凝抑制(hemagglutination inhibition,HI)、微量中和(microneutralization,MN)实验评价流感mRNA疫苗诱导小鼠产生的血清抗体滴度;通过流式细胞术评价Comb-mRNA疫苗诱导的细胞免疫反应。采用5LD_(50)野生型H1N1流感病毒株感染小鼠评价Comb-mRNA疫苗的免疫保护效果。结果成功构建mRNA-HA、mRNA-NP和mRNA-3M2e,且3种mRNA均能在293T细胞表达。脂质纳米颗粒包裹mRNA平均粒径为(119.53±6.5)nm,平均电位为(-8.23±1.3)mV。与LNP组比较,Comb-mRNA组疫苗的HI几何平均滴度(geometric mean titer,GMT)达179.6,MN的GMT达201.6,同时诱导IFNγ+CD4+/CD8+T细胞比例升高。Comb-mRNA组在加强免疫后2周能够提供对5LD_(50)野生流感H1N1亚型病毒的保护。结论通用流感疫苗候选疫苗Comb-mRNA能够诱导小鼠免疫反应并保护小鼠免受病毒感染。展开更多
基金supported by the National Natural Science Foundation of China (31970696, 81502975, 82188102, and 81830089)Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholar (LR22H160010)+2 种基金National Key Research and Development Program of China (2019YFC1316000)Zhejiang Provincial Key Research and Development Program (2019C03019)Zhejiang Provincial College Student Science and Technology Innovation Activity Plan-College Student Innovation and Entrepreneurship Incubation Program (Young Talent Program)(2022R40122)
文摘Pancreatic cancer is characterized by inter-tumoral and intra-tumoral heterogeneity,especially in genetic alteration and microenvironment.Conventional therapeutic strategies for pancreatic cancer usually suffer resistance,highlighting the necessity for personalized precise treatment.Cancer vaccines have become promising alternatives for pancreatic cancer treatment because of their multifaceted advantages including multiple targeting,minimal nonspecific effects,broad therapeutic window,low toxicity,and induction of persistent immunological memory.Multiple conventional vaccines based on the cells,microorganisms,exosomes,proteins,peptides,or DNA against pancreatic cancer have been developed;however,their overall efficacy remains unsatisfactory.Compared with these vaccine modalities,messager RNA(mRNA)-based vaccines offer technical and conceptional advances in personalized precise treatment,and thus represent a potentially cutting-edge option in novel therapeutic approaches for pancreatic cancer.This review summarizes the current progress on pancreatic cancer vaccines,highlights the superiority of mRNA vaccines over other conventional vaccines,and proposes the viable tactic for designing and applying personalized mRNA vaccines for the precise treatment of pancreatic cancer.
基金supported by the National Natural Science Foundation of China(31970696,81502975,81830089,U20A20378,82188102)the Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholar(LR22H160010)+2 种基金the National Key Research and Development Program(2019YFC1316000)the Zhejiang Provincial Key Research and Development Program(2019C03019)the Zhejiang Provincial College Student Science and Technology Innovation Activity Plan-College Student Innovation and Entrepreneurship Incubation Program(Young Talent Program)(2022R40122)。
文摘Cholangiocarcinoma(CHOL)is one of the most aggressive tumors worldwide and cannot be effectively treated by conventional and novel treatments,including immune checkpoint blockade therapy.The mRNA vaccine-based immunotherapeutic strategy has attracted much attention for various diseases,however,its application in CHOL is limited due to the thoughtlessness in the integration of vaccine design and patient selection.A recent study established an integrated path for identifying potent CHOL antigens for mRNA vaccine development and a precise stratification for identifying CHOL patients who can benefit from the mRNA vaccines.In spite of a promising prospect,further investigations should identify immunogenic antigens and onco-immunological characteristics of CHOL to guide the clinical application of CHOL mRNA vaccines in the future.
文摘BACKGROUND mRNA vaccines have been investigated in multiple tumors,but limited studies have been conducted on their use for hepatocellular carcinoma(HCC).AIM To identify candidate mRNA vaccine antigens for HCC and suitable subpopu-lations for mRNA vaccination.METHODS Gene expression profiles and clinical information of HCC datasets were obtained from International Cancer Genome Consortium and The Cancer Genome Atlas.Genes with somatic mutations and copy number variations were identified by cBioPortal analysis.The differentially expressed genes with significant prognostic value were identified by Gene Expression Profiling Interactive Analysis 2 website analysis.The Tumor Immune Estimation Resource database was used to assess the correlation between candidate antigens and the abundance of antigen-presenting cells(APCs).Tumor-associated antigens were overexpressed in tumors and associated with prognosis,genomic alterations,and APC infiltration.A consensus cluster analysis was performed with the Consensus Cluster Plus package to identify the immune subtypes.The weighted gene coexpression network analysis(WGCNA)was used to determine the candidate biomarker molecules for appropriate populations for mRNA vaccines.immune subtypes showed distinct cellular and clinical characteristics.The IS1 and IS3 immune subtypes were immunologically“cold”.The IS2 and IS4 immune subtypes were immunologically“hot”,and the immune checkpoint genes and immunogenic cell death genes were upregulated in these subtypes.IS1-related modules were identified with the WGCNA algorithm.Ultimately,five hub genes(RBP4,KNG1,METTL7A,F12,and ABAT)were identified,and they might be potential biomarkers for mRNA vaccines.CONCLUSION AURKA,CCNB1,CDC25C,CDK1,TRIP13,PES1,MCM3,PPM1G,NEK2,KIF2C,PTTG1,KPNA2,and PRC1 have been identified as candidate HCC antigens for mRNA vaccine development.The IS1 and IS3 immune subtypes are suitable populations for mRNA vaccination.RBP4,KNG1,METTL7A,F12,and ABAT are potential biomarkers for mRNA vaccines.
文摘BACKGROUND As of 31 December 2022,there were over 6.6 million coronavirus disease 2019(COVID-19)deaths and over 651 million cases across 200 countries worldwide.Despite the increase in vaccinations and booster shots,COVID-19 cases and deaths continue to remain high.While the effectiveness of these vaccines has already been established by different manufacturers,the fact remains that these vaccines were created quickly for global emergency use,tested under controlled clinical conditions from voluntary subjects and age groups whose general characteristics may differ from the actual general population.AIM To conduct a systematic review to determine the real-world effectiveness of mRNA COVID-19 vaccines in the elderly during the predominance of Delta and Omicron variants in preventing COVID-19 related infection,hospital,intensive care unit(ICU)admission and intubation,and death.METHODS A combination of Medical Subject Headings and non–Medical Subject Headings was carried out to identify all relevant research articles that meets the inclusion and exclusion criteria from PubMed,Cochrane,CINAHL,Scopus,ProQuest,EMBASE,Web of Science,and Google Scholar databases,as well as qualified research studies from pre–print servers using medRxiv and Research Square,published from January 1,2021-December 31,2022.RESULTS As per the inclusion and exclusion criteria,the effectiveness of Pfizer-BioNTech and Moderna vaccines were evaluated from an estimated total study population of 26535692 using infection,hospital,ICU admission and intubation,and death as outcome measures from studies published between 2021 and 2022,conducted in New York,Finland,Canada,Costa Rica,Qatar,Greece,and Brazil.The risk of bias was evaluated using risk of bias in nonrandomized studies of interventions(ROBINS-I)tool for cohort,case-control,and cross-sectional studies.While clinical trial data on Pfizer-BioNTech and Moderna vaccines demonstrated 94%vaccine effectiveness in the elderly,the results in this study showed that vaccine effectiveness in real-world settings is marginally lower against infection(40%-89%),hospitalization(92%),ICU admission and intubation(98%-85%),and death(77%-87%)with an indication of diminished effectiveness of vaccine over time.Furthermore,2 doses of mRNA vaccines are inadequate and only provides interim protection.CONCLUSION Because of the natural diminishing effectiveness of the vaccine,the need for booster dose to restore its efficacy is vital.From a research perspective,the use of highly heterogeneous outcome measures inhibits the comparison,contrast,and integration of the results which makes data pooling across different studies problematic.While pharmaceutical intervention like vaccination is important to fight an epidemic,utilizing common outcome measurements or carrying out studies with minimal heterogeneity in outcome measurements,is equally crucial to better understand and respond to an international health crisis.
基金support received from American University of Beirut(AUB)for their support and encouragement in carrying out this work.
文摘mRNA vaccines have emerged as promising alternative platforms to conventional vaccines.Their ease of production,low cost,safety profile and high potency render them ideal candidates for prevention and treatment of infectious diseases,especially in the midst of pandemics.The challenges that face in vitro transcribed RNA were partially amended by addition of tethered adjuvants or co-delivery of naked mRNA with an adjuvanttethered RNA.However,it wasn’t until recently that the progress made in nanotechnology helped enhance mRNA stability and delivery by entrapment in novel delivery systems of which,lipid nanoparticles.The continuous advancement in the fields of nanotechnology and tissue engineering provided novel carriers for mRNA vaccines such as polymeric nanoparticles and scaffolds.Various studies have shown the advantages of adopting mRNA vaccines for viral diseases and cancer in animal and human studies.Self-amplifying mRNA is considered today the next generation of mRNA vaccines and current studies reveal promising outcomes.This review provides a comprehensive overview of mRNA vaccines used in past and present studies,and discusses future directions and challenges in advancing this vaccine platform to widespread clinical use.
文摘For centuries,therapeutic cancer vaccines have been developed and tried clinically.Way back in the late 19th century,the Father of Immunotherapy,William Coley had discovered that bacterial toxins were effective for inoperable sarcomas.In the 1970s,the Bacillus Calmette-Guérin(BCG)vaccine was repurposed,e.g.,for advanced melanomas.Then,therapeutic cancer vaccines based on tumorassociated antigens(found on the surfaces of cancer cells)were tried clinically but apparently have not made a really significant clinical impact.For repurposed pathogen vaccines,only the BCG vaccine was approved in 1989 for local application to treat nonmuscle-invading bladder cancers.Although the mildly toxic vaccine adjuvants deliberately added to conventional pathogen vaccines are appropriate for seasonal applications,when repurposed for continual oncology usage,toxicity may be problematic.In 2010,even with the approval of sipuleucel-T as the very first cancer vaccine(dendritic cell)developed for designated prostate cancers,it has also not made a really significant clinical impact.Perhaps more"user friendly"cancer vaccines should be explored.As from approximately 30 years ago,the safety and effectiveness of mRNA vaccination for oncology had already been studied,the current coronavirus disease 2019 pandemic,though disastrous,has given such progressively advancing technology a kickstart.For oncology,other virtues of mRNA vaccines seem advantageous,e.g.,rapid and versatile development,convenient modular design,and entirely cell-free synthesis,are being progressively recognized.Moreover,mRNAs encoding various oncology antigens for vaccination may also be tested with the combination of relatively non-toxic modalities of oncology treatments,e.g.,metformin or metronomic(low-dose,prolonged administration)chemotherapy.Admittedly,robust clinical data obtained through good quality clinical trials are mandatory.
文摘BACKGROUND We present a rare case of status epilepticus in a 56-year-old man which arose as a complication after vaccination with the coronavirus disease 2019(COVID-19)mRNA-1273 vaccine.The patient's history included well-compensated secondary epilepsy.The root cause of the situation was a fever which had developed as a side effect of the vaccination.CASE SUMMARY A 56-year-old man received the first dose of mRNA-1273 vaccine against the severe acute respiratory syndrome-coronavirus-2.The vaccine was administered intramuscularly(100 mg,0.5 mL).The next morning the man was found to be suffering from fever and headaches while at the same time experiencing general weakness.He lost consciousness suddenly and experienced generalized clonic seizures which turned into status epilepticus.When the Emergency Medical Service arrived the patient was unconscious with spontaneous breathing and generalized clonic seizures.It was necessary to administer diazepam repeatedly.It was also necessary to administer high doses of levetiracetam and temporary propofol.The status epilepticus was brought under control approximately 90 min after the patient’s transport to the Emergency Department.A follow-up electroencephalogram no longer revealed abnormal indications of epileptic fit.The patient was temporarily hospitalized in the Intensive Care Unit and after seven days care was discharged without any further apparent effects.CONCLUSION There is currently no specific treatment against COVID-19.Therefore,the benefits of COVID-19 vaccine protection outweigh the risks.
文摘BACKGROUND A 70-year-old man with hepatitis C virus-related recurrent hepatocellular carcinoma was admitted for further diagnosis of a 1 cm iso-hyperechoic nodule in segment(S)5.CASE SUMMARY Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging(EOB-MRI)revealed the nodule in S5 with a defect at the hepatobiliary phase,hyperintensity on diffusion weighted imaging(DWI)and hypointensity on apparent diffusion coefficient(ADC)map.Contrast-enhanced computed tomography revealed hypervascularity at the early phase,and delayed contrast-enhancement was observed at the late phase.Contrast-enhanced ultrasound(US)revealed incomplete defect at the late vascular phase.Inflammatory liver tumor,lymphoproliferative disease,intrahepatic cholangiocarcinoma(small duct type)and bile duct adenoma were suspected through the imaging studies.US guided biopsy,however,showed a noncaseating hepatic sarcoid-like epithelioid granuloma(HSEG),and histopathological analysis disclosed spindle shaped epithelioid cells harboring Langhans-type multinucleated giant cells.One month after admission,EOB-MRI signaled the disappearance of the defect at the hepatobiliary phase,of hyperintensity on DWI,of hypointensity on ADC map,and no stain at the early phase.CONCLUSION That the patient had received BNT162b2 messenger RNA(mRNA)coronavirus disease 2019 vaccination 3 mo before the occurrence of HSEG,and that its disappearance was confirmed 4 mo after mRNA vaccination suggested that the drug-induced sarcoidosis-like reaction(DISR)might be induced by the mRNA vaccination.Fortunately,rechallenge of drug-induced DISR with the third mRNA vaccination was not confirmed.
文摘目的构建通用流感mRNA疫苗并全面评价其免疫保护效果。方法优化流感病毒株A/California/04/2009的血凝素(hemagglutinin,HA)、核蛋白(nucleoprotein,NP)和基质蛋白2胞外区(matrix protein 2 ectodomain,M2e)抗原序列,并将HA、NP和3个串联的M2e(3M2e)分别克隆至pcDNA3.1载体,通过线性化、体外转录、酶学法加帽、酶促加尾合成mRNA,命名为mRNA-HA、mRNA-NP和mRNA-3M2e。3种mRNA分别转染293T细胞后,通过免疫荧光实验鉴定蛋白的表达。利用脂质纳米颗粒分别包裹mRNA-HA、mRNA-NP和mRNA-3M2e并测量其粒径和电位。再将3种mRNA等体积混合制备成Comb-mRNA疫苗。将28只6周雌性Balb/c小鼠(体质量为18~22 g)按简单随机分组法分为2组:LNP组(n=14)和Comb-mRNA组(n=14)。通过血凝抑制(hemagglutination inhibition,HI)、微量中和(microneutralization,MN)实验评价流感mRNA疫苗诱导小鼠产生的血清抗体滴度;通过流式细胞术评价Comb-mRNA疫苗诱导的细胞免疫反应。采用5LD_(50)野生型H1N1流感病毒株感染小鼠评价Comb-mRNA疫苗的免疫保护效果。结果成功构建mRNA-HA、mRNA-NP和mRNA-3M2e,且3种mRNA均能在293T细胞表达。脂质纳米颗粒包裹mRNA平均粒径为(119.53±6.5)nm,平均电位为(-8.23±1.3)mV。与LNP组比较,Comb-mRNA组疫苗的HI几何平均滴度(geometric mean titer,GMT)达179.6,MN的GMT达201.6,同时诱导IFNγ+CD4+/CD8+T细胞比例升高。Comb-mRNA组在加强免疫后2周能够提供对5LD_(50)野生流感H1N1亚型病毒的保护。结论通用流感疫苗候选疫苗Comb-mRNA能够诱导小鼠免疫反应并保护小鼠免受病毒感染。