Reactive amanitin for bioconjugation to antibodies**

该提案与Iprogen， Inc.（一家致力于生产抗体-药物偶联物（adc）的生物制药公司）合作，解决了癌症靶向治疗中未满足的需求。Iprogen的战略定位是利用新型弹头创造新的靶向疗法。我的实验室准备为益普罗根提供基于amanitin的新弹头。针对癌症的靶向治疗是一种快速发展的抗癌药物，它使用癌症特异性靶向剂（如抗体）向癌细胞传递一种有效的，但通常是非特异性的细胞毒性药物。单独的抗体或多肽通常是无效的，但当与一种合适的毒素结合时，就会对癌症有效，否则这种毒素的毒性就太大了。adc现在给癌症患者带来了明确的希望。然而，在工业转化方面，对于可以针对癌症的新型有毒有效载荷以及生产用于测试和临床转化的新adc的手段的需求仍未得到满足。****我的实验室，专门从事生物偶联和天然产物合成，最近完成了第一次全合成amanitin，一种有效的有效载荷毒素，用于ADC的开发。Iprogen, Inc.是一家成立于不列颠哥伦比亚省里士满的生物技术公司，致力于为临床前和临床应用开发新的抗体-药物偶联物。这项资助将在我的实验室的研究兴趣和Iprogen的商业利益之间形成独特的研究协同作用，我们将开发新的基于amanitin的毒性有效载荷，将这些毒素应用于各种治疗性抗体，以基于它们与减轻疾病的抗体的结合创造新的知识产权。我的实验室将为Iprogen的科学家提供所需的有效载荷毒素和新型连接臂技术。反过来，Iprogen的工作人员科学家将生成新的adc，并将在适当的毒性分析中对其进行测试**

This proposal addresses unmet needs in targeted therapy for cancer in collaboration with Iprogen, Inc. a biopharmaceutical company dedicated to the production of antibody-drug conjugates (ADCs). Iprogen is strategically positioned to create new targeted therapies from novel warheads. My lab is poised to provide Iprogen with new warheads based on amanitin. Targeted therapies for cancer represent a rapidly expanding class of anticancer agents that use a cancer-specific targeting agent (e.g. an antibody) to deliver a potent, but usually non-specific, cytotoxic agent to cancer cells. Antibodies or peptides alone are often ineffective but become effective against cancer when conjugated to a suitable toxin that otherwise would be too toxic. ADCs now offer definitive hope to cancer patients. Yet in terms of industrial translation, there is a significant unmet need for new toxic payloads that that can be targeted to cancer as well as a means of producing new ADCs for testing and clinical translation. ****My lab, which specializes in bioconjugation and natural product synthesis, has recently accomplished the first total synthesis of amanitin, a potent and validated payload toxin for ADC development. Iprogen, Inc. is an established biotechnology company in Richmond, B.C., with an interest in generating new antibody-drug conjugates for preclinical and clinical applications. This Engage Grant will forge a unique research synergy between my lab's research interest where we will develop new amanitin-based toxic payloads and Iprogen's commercial interests in applying these toxins to various therapeutic antibodies to create new IP based on their conjugation to diseased-mitigating antibodies. My lab will provide scientists at Iprogen with the needed payload toxins and novel linker-arm technologies. In turn, staff scientists at Iprogen will generate new ADCs and will test them in suitable toxicity assays**