The antibody-drug conjugates (ADCs) are one the fastest growing biotherapeutics in oncology and are still in their infancy in gastrointestinal (GI) cancer for clinical applications to improve patient survival. The ADC based approach is developed with tumor specific antigen, antibody carrying cytotoxic agents to precisely target and deliver chemotherapeutics at the tumor site. To date, 11 ADCs have been approved by US-FDA, and more than 80 are in the clinical development phase for different oncological indications. However, The ADCs based therapies in GI cancers are still far from having high-efficient clinical outcomes. The limited success of these ADCs and lessons learned from the past are now being used to develop a newer generation of ADC against GI cancers. In this review, we did a comprehensive assessment of the key components of ADCs, including tumor marker, antibody, cytotoxic payload, and linkage strategy, with a focus on technical improvement and some future trends in the pipeline for clinical translation. The various preclinical and clinical ADCs used in gastrointestinal malignancies, their target, composition and bioconjugation, along with preclinical and clinical outcomes, are discussed. The emphasis is also given to new generation ADCs employing novel mAb, payload, linker, and bioconjugation methods are also included.

抗体-药物偶联物 (ADC) 是肿瘤学中发展最快的生物治疗剂之一，在胃肠道 (GI) 癌症的临床应用中仍处于起步阶段，以提高患者的生存率。基于 ADC 的方法是使用肿瘤特异性抗原、携带细胞毒剂的抗体开发的，以在肿瘤部位精确靶向和递送化疗药物。迄今为止，已有 11 种 ADC 获得美国 FDA 的批准，超过 80 种处于不同肿瘤适应症的临床开发阶段。然而，基于 ADC 的胃肠道癌症疗法仍远未达到高效的临床结果。这些 ADC 的有限成功和从过去吸取的经验教训现在被用于开发新一代的 ADC 来对抗胃肠道癌症。在这次审查中，我们对 ADC 的关键组成部分进行了全面评估，包括肿瘤标志物、抗体、细胞毒性有效载荷和连锁策略，重点是技术改进和临床转化管道的一些未来趋势。讨论了用于胃肠道恶性肿瘤的各种临床前和临床 ADC、它们的靶点、组成和生物偶联，以及临床前和临床结果。还重点介绍了采用新型 mAb、有效载荷、接头和生物偶联方法的新一代 ADC。