1.A novel shark VNAR antibody-based immunotoxin targeting TROP-2 for cancer therapy.
Xiaozhi XI ; Yanqing WANG ; Guiqi AN ; Shitao FENG ; Qiumei ZHU ; Zhongqiu WU ; Jin CHEN ; Zhicheng ZUO ; Qiang WANG ; Ming-Wei WANG ; Yuchao GU
Acta Pharmaceutica Sinica B 2024;14(11):4806-4818
TROP-2, a tumor-associated antigen, has been implicated in the progression of various epithelial tumors. Due to its favorable expression profile, TROP-2 has emerged as a promising target for antibody-drug conjugates (ADCs) based anti-tumor therapies. Although ADCs have shown efficacy in cancer treatment, their application in solid tumors is hindered by their high molecular weight, poor tumor penetration, and release of cytotoxic molecules. Therefore, a recombinant immunotoxin was developed based on a shark-derived variable domain of immunoglobulin new antigen receptor (VNAR) antibody. VNARs are only one-tenth the size of IgG antibodies and possess remarkable tissue penetration capabilities and high stability. In this study, a shark VNAR phage display library was created, leading to the identification of shark VNAR-5G8 that targets TROP-2. VNAR-5G8 exhibited a high affinity and cellular internalization ability towards cells expressing high levels of TROP-2. Epitope analysis revealed that VNAR-5G8 recognizes a hidden epitope consisting of CRD and TY-1 on TROP-2. Subsequently, VNAR-5G8 was fused with a truncated form of Pseudomonas exotoxin (PE38) to create the recombinant immunotoxin (5G8-PE38), which exhibited significant anti-tumor activity in vitro and in vivo. Overall, this study highlights the promise of 5G8-PE38 as a valuable candidate for cancer therapy.
2.Diagnosis and treatment of Chiari malformation type 1 in children: interpretation on international consensus document (2021)
Meng WANG ; Yan HU ; Yuchao ZUO ; Peichao ZHAO ; Fuyou GUO
Chinese Journal of Neuromedicine 2022;21(8):757-761
Chiari malformation type 1 (CM1) is a rare condition where agreed classification and treatment are still missing. In 2019, 34 international experts from Europe achieved a consensus on the definition, diagnosis, and treatment of CM1 in children, aiming to guide the clinical diagnosis and treatment of CM1 in children. Now the consensus is interpreted based on recent international research achievements, aiming to provide references for accurate clinical assessment and individualized treatment of CM1 in children.
3.Diagnosis and treatment of Chiari malformation and syringomyelia in adults: an interpretation of international consensus document (2021)
Meng WANG ; Yan HU ; Yuchao ZUO ; Peichao ZHAO ; Fuyou GUO
Chinese Journal of Neuromedicine 2022;21(9):865-869
Chiari malformation (CM) is the most common cause of syringomyelia, where agreed criterions on classification and treatment are still missing. In 2019, 29 international experts from Europe achieved a consensus on the definition, classification, diagnosis and treatment of CM and syringomyelia in adults, aiming to guide the clinical diagnosis and treatment of these diseases. Now the consensus is interpreted based on recently published literature at home and abroad, aiming to provide references for standardized diagnosis and treatment of CM and syringomyelia in adults.
4.Diagnosis and treatment of Chiari malformation and syringomyelia in adults: an interpretation of international consensus document (2021)
Meng WANG ; Yan HU ; Yuchao ZUO ; Peichao ZHAO ; Fuyou GUO
Chinese Journal of Neuromedicine 2022;21(9):865-869
Chiari malformation (CM) is the most common cause of syringomyelia, where agreed criterions on classification and treatment are still missing. In 2019, 29 international experts from Europe achieved a consensus on the definition, classification, diagnosis and treatment of CM and syringomyelia in adults, aiming to guide the clinical diagnosis and treatment of these diseases. Now the consensus is interpreted based on recently published literature at home and abroad, aiming to provide references for standardized diagnosis and treatment of CM and syringomyelia in adults.

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