Dear Editor,CLDN18.2(CLDN),a member of tight junction protein family,is strictly limited to express on differentiated epithelial cells of the gastric mucosa and abnormal overexpression has been found in many cancers,e...Dear Editor,CLDN18.2(CLDN),a member of tight junction protein family,is strictly limited to express on differentiated epithelial cells of the gastric mucosa and abnormal overexpression has been found in many cancers,especially in digestive system malignancies.1 Those features make CLDN a potential therapeutic target.However,monoclonal antibody targeting CLDN induce limited antitumor immune responses in clinical trials and fusion of strong immunomodulators might be needed to enhance its efficacy.High dose IL-2 activates tumor infiltrating lymphocytes(TILs),but the severe toxicity and poor tumor targeting limits its use.展开更多
Lack of an appropriate small animal model remains a major hurdle for studying the immunotolerance and immunopathogenesis induced by hepatitis B virus （HBV） infection. In this study, we report a mouse model with sust...Lack of an appropriate small animal model remains a major hurdle for studying the immunotolerance and immunopathogenesis induced by hepatitis B virus （HBV） infection. In this study, we report a mouse model with sustained HBV viremia after infection with a recombinant adeno-associated virus （AAV） carrying a replicable HBV genome （AAV/ HBV）. Similar to the clinical HBV carriers, the mice infected with AAV/H BV were sero-negative for antibodies against HBV surface antigen （HBsAg）. Immunization with the conventional HBV vaccine in the presence of aluminum adjuvant failed to elicit an immune response against HBV in these mice. To identify a vaccine that can potentially circumvent this tolerance, the TLR9 agonist CpG was added to HBsAg as an adjuvant. Vaccination of mice with HBsAg/CpG induced not only clearance of viremia, but also strong antibody production and T-cell responses. Furthermore, both the DNA replication and protein expression of HBV were significantly reduced in the livers of AAV/H BV-infected mice. Accordingly, AAV/HBV-infected mice may be used as a robust model for investigating the underlying mechanism（s） of HBV immunotolerance and for developing novel immunotherapies to eradicate HBV infections.展开更多
Antibodies,as one of the most important components of host adaptive immune system,play an important role in defense of infectious disease,immune surveillance,and autoimmune disease.Due to the development of recombinan...Antibodies,as one of the most important components of host adaptive immune system,play an important role in defense of infectious disease,immune surveillance,and autoimmune disease.Due to the development of recombinant antibody technology,antibody therapeutics become the largest and rapidly expanding drug to provide major health benefits to patients,especially for the treatment of cancer patients.Many antibody-based therapeutic strategies have been developed including monoclonal anti-bodies,antibody-drug conjugates,bispecific and trispecific antibodies and pro-antibodies with promising results from both clinical and pre-clinical trials.However,the response rate and side-effect still vary between patients with undefined mechanisms.Here,we summarized the current and future perspectives of antibody-based cancer immunotherapeutic strategies for designing next-generation drugs.展开更多
基金This work was supported by Cancer Prevention and Research Institute of Texas(CPRIT)grant RR150072 given to Y.-X.Fthe NIH/NCI grant R01-CA240952 given to J.Q.National Natural Science Foundation of China 82250710684 to Y.F.The funders had no role in study design,data collection and analysis,decision to publish or preparation of the manuscript.We thank the Institutional Animal Care and Use Committee Animal Resources Center,and Animal Research Center.We also thank Z.R,Y.L.,C.M.,E.H.and B.Moon for providing experiment materials and helpful discussions.
文摘Dear Editor,CLDN18.2(CLDN),a member of tight junction protein family,is strictly limited to express on differentiated epithelial cells of the gastric mucosa and abnormal overexpression has been found in many cancers,especially in digestive system malignancies.1 Those features make CLDN a potential therapeutic target.However,monoclonal antibody targeting CLDN induce limited antitumor immune responses in clinical trials and fusion of strong immunomodulators might be needed to enhance its efficacy.High dose IL-2 activates tumor infiltrating lymphocytes(TILs),but the severe toxicity and poor tumor targeting limits its use.
文摘Lack of an appropriate small animal model remains a major hurdle for studying the immunotolerance and immunopathogenesis induced by hepatitis B virus （HBV） infection. In this study, we report a mouse model with sustained HBV viremia after infection with a recombinant adeno-associated virus （AAV） carrying a replicable HBV genome （AAV/ HBV）. Similar to the clinical HBV carriers, the mice infected with AAV/H BV were sero-negative for antibodies against HBV surface antigen （HBsAg）. Immunization with the conventional HBV vaccine in the presence of aluminum adjuvant failed to elicit an immune response against HBV in these mice. To identify a vaccine that can potentially circumvent this tolerance, the TLR9 agonist CpG was added to HBsAg as an adjuvant. Vaccination of mice with HBsAg/CpG induced not only clearance of viremia, but also strong antibody production and T-cell responses. Furthermore, both the DNA replication and protein expression of HBV were significantly reduced in the livers of AAV/H BV-infected mice. Accordingly, AAV/HBV-infected mice may be used as a robust model for investigating the underlying mechanism（s） of HBV immunotolerance and for developing novel immunotherapies to eradicate HBV infections.
文摘Antibodies,as one of the most important components of host adaptive immune system,play an important role in defense of infectious disease,immune surveillance,and autoimmune disease.Due to the development of recombinant antibody technology,antibody therapeutics become the largest and rapidly expanding drug to provide major health benefits to patients,especially for the treatment of cancer patients.Many antibody-based therapeutic strategies have been developed including monoclonal anti-bodies,antibody-drug conjugates,bispecific and trispecific antibodies and pro-antibodies with promising results from both clinical and pre-clinical trials.However,the response rate and side-effect still vary between patients with undefined mechanisms.Here,we summarized the current and future perspectives of antibody-based cancer immunotherapeutic strategies for designing next-generation drugs.
