Zhao Zihan, Wu Xiangyu, Zhang Tianyang, Zhou Meng, Liu Siyang, Yang Rong, Li Jie P
Department of Urology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Rd, Nanjing, Jiangsu, 210008, China.
State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering Nanjing University, 163 Xianlin Avenue, Nanjing, Jiangsu, 210023, China.
Chembiochem. 2025 Feb 1;26(3):e202400731. doi: 10.1002/cbic.202400731. Epub 2025 Jan 23.
The evolution of antitumor drug development has transitioned from single-agent chemotherapy to targeted therapy, immunotherapy, and more recently, multispecific drugs. These innovative drugs target multiple cellular or molecular pathways simultaneously, offering a more comprehensive anticancer approach and addressing some of the limitations inherent in traditional monotherapies. However, preclinical assessment of multispecific drugs remains challenging, as conventional tumor models often lack the necessary complexity to accurately reflect the interactions between various cell types and targets. Patient-derived immunocompetent tumor organoids (PDITOs), which incorporate both tumor cells and immune cells, present a promising platform for the evaluation of these drugs. Beyond their use in drug evaluation, PDITOs can also be utilized in personalized drug screening and predicting patient-specific treatment outcomes, thus advancing both multispecific drug development and precision medicine. This perspective discusses the current landscape of multispecific drug development and the methodologies for constructing PDITOs. It also addresses the associated challenges and introduces the concept of employing these organoids to optimize the evaluation and rational design of multispecific drug therapies.
抗肿瘤药物研发的演变已从单药化疗过渡到靶向治疗、免疫治疗，以及最近的多特异性药物。这些创新药物同时靶向多个细胞或分子途径，提供了一种更全面的抗癌方法，并解决了传统单一疗法固有的一些局限性。然而，多特异性药物的临床前评估仍然具有挑战性，因为传统的肿瘤模型往往缺乏必要的复杂性，无法准确反映各种细胞类型和靶点之间的相互作用。包含肿瘤细胞和免疫细胞的患者来源的具有免疫活性的肿瘤类器官（PDITOs）为评估这些药物提供了一个有前景的平台。除了用于药物评估外，PDITOs还可用于个性化药物筛选和预测患者特异性治疗结果，从而推动多特异性药物研发和精准医学的发展。本观点讨论了多特异性药物研发的现状以及构建PDITOs的方法。它还探讨了相关挑战，并介绍了利用这些类器官优化多特异性药物治疗评估和合理设计的概念。
