Heinrich Bernd, Greten Tim F
Klinik für Gastroenterologie, Hepatologie, Infektiologie und Endokrinologe, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Deutschland.
Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 20892 Bethesda, MD USA.
Gastroenterologie. 2025;20(3):199-207. doi: 10.1007/s11377-025-00895-y. Epub 2025 Apr 4.
Immunotherapy is part of the standard therapy for gastrointestinal (GI) tumors. Nevertheless, response rates are rather low. Current studies are investigating the optimal timing and patient clientele for immunotherapy. Combinations of approved drugs are also being tested. The development of new therapeutic approaches is equally important, e.g. to overcome primary and secondary resistance. Antibody-mediated immune checkpoint inhibitor (ICI) therapy is constantly being expanded. New target molecules on immune and tumor cells are intended to further improve the immune response by activating immune cells or blocking an inhibitory signaling pathway. The combination of antibody with drug in the sense of an immunoconjugate is possible. Modifications of the antibody structure are being tested for improved efficacy and an extended range of applications. Cellular strategies, such as adoptive cell transfer or the application of genetically modified T cells, are currently being tested in studies for use in GI tumors. T cells with chimeric antigen receptors (CAR), which recognize and attack certain proteins on tumor cells, are a promising approach. Viruses that can destroy tumor cells due to natural reproductive behavior or genetic alterations are used as oncolytic viruses in GI oncology, but pose challenges due to low immunogenicity or non-specific effects. Another difficulty is the development of sensitive and specific biomarkers that predict response and efficacy of immunotherapies. This review article aims to provide a glimpse into the crystal ball and present and discuss new promising immunotherapeutic approaches.
免疫疗法是胃肠道(GI)肿瘤标准治疗的一部分。然而,缓解率相当低。目前的研究正在调查免疫疗法的最佳时机和适用患者群体。已获批药物的联合使用也在进行测试。开发新的治疗方法同样重要,例如克服原发性和继发性耐药。抗体介导的免疫检查点抑制剂(ICI)疗法正在不断扩展。免疫细胞和肿瘤细胞上的新靶分子旨在通过激活免疫细胞或阻断抑制性信号通路来进一步改善免疫反应。抗体与药物以免疫缀合物的形式联合使用是可行的。正在测试抗体结构的修饰以提高疗效和扩大应用范围。细胞策略,如过继性细胞转移或应用基因改造的T细胞,目前正在胃肠道肿瘤研究中进行测试。具有嵌合抗原受体(CAR)的T细胞能够识别并攻击肿瘤细胞上的某些蛋白质,是一种很有前景的方法。由于天然繁殖行为或基因改变而能够破坏肿瘤细胞的病毒在胃肠道肿瘤学中用作溶瘤病毒,但由于免疫原性低或非特异性作用而带来挑战。另一个难题是开发能够预测免疫疗法反应和疗效的敏感且特异的生物标志物。这篇综述文章旨在展望未来,介绍并讨论新的有前景的免疫治疗方法。