Amanita phalloides is the primary species responsible for fatal mushroom poisoning, as its main toxin, α-amanitin, irreversibly and potently inhibits eukaryotic RNA polymerase II (RNAP II), leading to cell death. There is no specific antidote for α-amanitin, which hinders its clinical application. However, with the advancement of precision medicine in oncology, including the development of antibody–drug conjugates (ADCs), the potential value of various toxic small molecules has been explored. These ADCs ingeniously combine the targeting precision of antibodies with the cytotoxicity of small-molecule payloads to precisely kill tumor cells. We searched PubMed for studies in this area using these MeSH terms “Amanitins, Alpha-Amanitin, Therapeutic use, Immunotherapy, Immunoconjugates, Antibodies” and did not limit the time interval. Recent studies have conducted preclinical experiments on ADCs based on α-amanitin, showing promising therapeutic effects and good tolerance in primates. The current challenges include the not fully understood toxicological mechanism of α-amanitin and the lack of clinical studies to evaluate the therapeutic efficacy of ADCs developed based on α-amanitin. In this article, we will discuss the role and therapeutic efficacy of α-amanitin as an effective payload in ADCs for the treatment of various cancers, providing background information for the research and application strategies of current and future drugs.

鹅膏菌是导致致命蘑菇中毒的主要物种，因为其主要毒素 α-鹅膏菌素可不可逆地有效抑制真核 RNA 聚合酶 II (RNAP II)，导致细胞死亡。 α-鹅膏蕈碱尚无特效解毒剂，阻碍了其临床应用。然而，随着肿瘤学精准医学的进步，包括抗体药物偶联物（ADC）的发展，各种有毒小分子的潜在价值已被探索。这些ADC巧妙地将抗体的靶向精度与小分子有效负载的细胞毒性结合起来，精确杀死肿瘤细胞。我们使用 MeSH 术语“鹅膏菌素、α-鹅膏菌素、治疗用途、免疫疗法、免疫缀合物、抗体”在 PubMed 中搜索该领域的研究，并且不限制时间间隔。最近的研究对基于α-鹅膏蕈碱的ADC进行了临床前实验，在灵长类动物中显示出良好的治疗效果和良好的耐受性。目前的挑战包括α-鹅膏蕈碱的毒理学机制尚未完全了解，以及缺乏评估基于α-鹅膏蕈碱开发的ADC的治疗效果的临床研究。在本文中，我们将讨论α-鹅膏蕈碱作为ADC中有效负载在治疗各种癌症中的作用和疗效，为当前和未来药物的研究和应用策略提供背景信息。