Antibody venom conjugates

抗体药物偶联物（adc）是一类结合抗体和药物有效载荷的新兴药物。该抗体将药物载荷靶向到特定的靶向细胞，提高了安全性和有效性。迄今为止，FDA批准的8种ADC药物均用于肿瘤小分子药物。尽管这些小分子adc具有比非靶向小分子药物更好的疗效和安全性，但越来越明显的是，它们屈服于癌细胞同样的多药耐药。在这个项目中，我们正在探索合成和评估更大分子的周期肽毒素药物，癌细胞将无法产生耐药性。该提案结合了Perrin实验室在新型毒液衍生肽与抗体生物偶联方面的独特化学培训成果，以及与温哥华新兴生物制药公司iProgen的工业合作伙伴关系。在较短的时间内，我们已经确定了一名具有多肽经验并准备参与该项目的合格博士后。传统上，由于各种全身毒性，这些环肽毒素很少用于肿瘤学应用；然而，通过利用ADC平台，我们假设这类新的毒素可能代表了一种重要的、尚未开发的抗癌药物有效载荷。Perrin实验室在环肽和双环肽的合成和评估方面拥有丰富的经验，包括阳环苷和amanitins的合成，这些都展示了该领域的专业知识，并且作为毒素代表了我们开发新的毒性支架作为adc有效载荷的备用分子。结果将是一流的化学结合毒素抗体的组合物，将由我们的工业合作伙伴iProgen在体外验证。

Antibody Drug Conjugates (ADCs) are an emerging class of drugs that combines antibody and drug payload. The antibody targets the drug payload to specific targeted cells improving both safety and efficacy. To date that are 8 FDA approved ADC drugs all for oncology application using small molecule drugs. Although these ADCs with small molecules encompasses superior efficacy and safety than non-targeted small molecule drugs, it is increasingly evident that they succumb to the same multi-drug resistance by the cancer cells. In this project, we are exploring the synthesis and evaluation of larger molecule cyclical peptide toxin drugs that cancer cells will not be able to develop resistance to. This proposal merges unique chemical training outcomes in the Perrin lab on bioconjugation of novel venom-derived peptides to antibodies with an industrial partnership with iProgen, an emerging biopharmaceutical company in Vancouver. With a short time-frame, we have identified a qualified postdoctoral fellow who has experience in peptides and is prepared to engage in this project.Traditionally, these cyclic peptide toxins are rarely used for oncology application due to a variety of systemic toxicity; however, by utilizing an ADC platform, we hypothesize that this new class of toxins may represent an important and untapped class of anti-cancer drug payloads to be unlocked. The Perrin lab has extensive experience in the synthesis and evaluation of cyclic and bicyclic peptides including the synthesis of both phalloidins and amanitins, which showcase know-how in this domain and as toxins represent back-up molecules as we advance new toxic scaffolds as payloads for ADCs. Outcomes will be first-in-class compositions of chemically conjugated toxins to antibodies that will be validated in vitro by our industrial partner, iProgen.