免疫缀合物是将抗体与不同试剂结合的有前途的分子,比如毒素,毒品,放射性核素,或主要针对肿瘤细胞的细胞因子。然而,肿瘤微环境(TME),它包含一个由各种细胞和分子线索组成的复杂网络,指导肿瘤的生长和进展,仍然是有效癌症治疗的主要挑战。我们的综述强调了TME在免疫缀合物治疗癌症中的关键作用,检查与TME的复杂相互作用以及TME靶向免疫缀合物的最新进展。我们探索针对TME组件的策略,利用不同的抗体,如中和,免疫调节,免疫检查点抑制剂,免疫刺激,和双特异性抗体。此外,我们讨论不同的免疫缀合物,阐明它们的作用机制,优势,局限性,以及在癌症免疫疗法中的应用。此外,我们强调提高免疫缀合物的安全性和有效性的新兴技术,如抗体工程,联合疗法,和纳米技术。最后,我们总结当前的进步,观点,以及TME靶向免疫缀合物的未来发展。
Immunoconjugates are promising molecules combining antibodies with different agents, such as toxins, drugs, radionuclides, or cytokines that primarily aim to target tumor cells. However, tumor microenvironment (TME), which comprises a complex network of various cells and molecular cues guiding tumor growth and progression, remains a major challenge for effective cancer therapy. Our review underscores the pivotal role of TME in cancer therapy with immunoconjugates, examining the intricate interactions with TME and recent advancements in TME-targeted immunoconjugates. We explore strategies for
targeting TME components, utilizing diverse antibodies such as neutralizing, immunomodulatory, immune checkpoint inhibitors, immunostimulatory, and bispecific antibodies. Additionally, we discuss different immunoconjugates, elucidating their mechanisms of action, advantages, limitations, and applications in cancer immunotherapy. Furthermore, we highlight emerging technologies enhancing the safety and efficacy of immunoconjugates, such as antibody engineering, combination therapies, and nanotechnology. Finally, we summarize current advancements, perspectives, and future developments of TME-targeted immunoconjugates.