The CoVID-19 pandemic that started in late 2019 is sweeping through the world,posing historic challenges to global health,and disrupting social and economic lives.Previous and recent studies indicate that monoclonal a...The CoVID-19 pandemic that started in late 2019 is sweeping through the world,posing historic challenges to global health,and disrupting social and economic lives.Previous and recent studies indicate that monoclonal antibodies can be efficacious in preventing and treating SARSCoV-1 and SARS-CoV-2 infections.Using a phage display platform,we have identified dozens of monoclonal antibodies that bind to diverse epitope groups on the SARS-CoV-2 spike protein.Many of them bound to the receptor binding domain(RBD)and inhibited ACE2-RBD interaction.展开更多
T cell engaging bispecific antibody(TCB)is an effective immunotherapy for cancer treatment.Through co-targeting CD3 and tumor-associated antigen(TAA),TCB can redirect CD3+T cells to eliminate tumor cells regardless of...T cell engaging bispecific antibody(TCB)is an effective immunotherapy for cancer treatment.Through co-targeting CD3 and tumor-associated antigen(TAA),TCB can redirect CD3+T cells to eliminate tumor cells regardless of the specificity of T cell receptor.Tissue factor(TF)is a TAA that involved in tumor progression.Here,we designed and characterized a novel TCB targeting TF(TF-TCB)for the treatment of TF-positive tumors.In vitro,robust T cell activation,tumor cell lysis and T cell proliferation were induced by TF-TCB.The tumor cell lysis activity was dependent upon both CD3 and TF binding moieties of the TF-TCB,and was related to TF expression level of tumor cells.In vivo,in both tumor cell/human peripheral blood mononuclear cells(PBMC)co-grafting model and established tumor models with poor T cell infiltration,tumor growth was strongly inhibited by TF-TCB.T cell infiltration into tumors was induced during the treatment.Furthermore,efficacy of TF-TCB was further improved by combination with immune checkpoint inhibitors.For the first time,our results validated the feasibility of using TF as a target for TCB and highlighted the potential for TF-TCB to demonstrate efficacy in solid tumor treatment.展开更多
基金the National Natural Science Foundation of China(No.81773621,82073751 to JZ)the National Science and Technology Major Project"Key New Drug Creation and Manufacturing Program"of China(No.2019ZX09732001-019 to JZ)+1 种基金the Key R&D Supporting Program(Special support for developing medicine for infectious diseases)from the Administration of Chinese and Singapore Tianjin Eco-city to Jecho Biopharmaceuticals Ltd.Co.,Zhejiang University special CoVID-19 grant 2020XGZX099Shanghai Jiao Tong University"Crossing Medical and Engineering"grant 20X190020003 to JZ.
文摘The CoVID-19 pandemic that started in late 2019 is sweeping through the world,posing historic challenges to global health,and disrupting social and economic lives.Previous and recent studies indicate that monoclonal antibodies can be efficacious in preventing and treating SARSCoV-1 and SARS-CoV-2 infections.Using a phage display platform,we have identified dozens of monoclonal antibodies that bind to diverse epitope groups on the SARS-CoV-2 spike protein.Many of them bound to the receptor binding domain(RBD)and inhibited ACE2-RBD interaction.
基金This work was supported by the National Natural Science Foundation of China(Nos.81773621 and 82073751)the National Science and Technology Major Project(No.2019ZX09201001,China).
文摘T cell engaging bispecific antibody(TCB)is an effective immunotherapy for cancer treatment.Through co-targeting CD3 and tumor-associated antigen(TAA),TCB can redirect CD3+T cells to eliminate tumor cells regardless of the specificity of T cell receptor.Tissue factor(TF)is a TAA that involved in tumor progression.Here,we designed and characterized a novel TCB targeting TF(TF-TCB)for the treatment of TF-positive tumors.In vitro,robust T cell activation,tumor cell lysis and T cell proliferation were induced by TF-TCB.The tumor cell lysis activity was dependent upon both CD3 and TF binding moieties of the TF-TCB,and was related to TF expression level of tumor cells.In vivo,in both tumor cell/human peripheral blood mononuclear cells(PBMC)co-grafting model and established tumor models with poor T cell infiltration,tumor growth was strongly inhibited by TF-TCB.T cell infiltration into tumors was induced during the treatment.Furthermore,efficacy of TF-TCB was further improved by combination with immune checkpoint inhibitors.For the first time,our results validated the feasibility of using TF as a target for TCB and highlighted the potential for TF-TCB to demonstrate efficacy in solid tumor treatment.
