CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Tumor-Infiltrating Lymphocytes, CAR-, and T-Cell Receptor-Modified T Cells in Solid Cancer Oncology.
Tumor-Infiltrating Lymphocytes, CAR-, and T-Cell Receptor-Modified T Cells in Solid Cancer Oncology.
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ACT 试验取得的进展将难治性实体癌免疫治疗领域推向了一个新阶段,其不断纳入新策略以开发下一代疗法,旨在增强疗效、提高安全性,并使大量患者能够更广泛地获得治疗。
过继性细胞治疗(ACT)是一种有前景的治疗方法,旨在增强T细胞抗肿瘤免疫反应。ACT包括TIL(肿瘤浸润淋巴细胞)、嵌合抗原受体(CAR)和T细胞受体基因修饰的T细胞。尽管CAR-T 细胞在血液系统恶性肿瘤中取得了里程碑式的成就,但ACT在难治性实体癌中显示出有限的临床反应,持久缓解仍仅限于少数患者。总结:在这篇综述中,我们重点介绍了T细胞疗法治疗实体癌的主要进展、局限性和当前发展。我们讨论了新兴的有前景的策略作为下一代ACT,探索局部递送途径以最大化疗效并提高安全性,整合预测性生物标志物以优化最可能从ACT中获益的患者选择,使用联合治疗以克服免疫抑制性肿瘤微环境,靶向多种肿瘤抗原以避免肿瘤抗原逃逸,选择最有效的T细胞产品以克服T细胞功能障碍,并结合尖端新技术,如基因编辑,以进一步改善抗肿瘤T细胞功能并减少治疗相关毒性。
BACKGROUND: Adoptive cellular therapy (ACT) is a promising treatment approach aiming at enhancing T-cell antitumor immune response. ACT includes tumor-infiltrating lymphocytes, chimeric antigen receptor (CAR) and T-cell receptor gene-modified T cells. Despite a milestone achievement with CAR-T cells in hematopoietic malignancies, ACT has shown modest clinical responses in refractory solid cancers and durable responses remain limited to a minor fraction of patients. SUMMARY: In this review, we highlight major advances, limitations and current developments of T-cell therapies for solid cancers. We discuss emerging promising strategies as next-generation ACT, exploring local delivery routes to maximize efficacy and improve safety, integrating predictive biomarkers to optimize selection of patients who most likely would benefit from ACT, using combination therapy to overcome the immunosuppressive tumor microenvironment, targeting multiple tumor antigen to avoid tumor antigen escape, selection of the most potent T-cell product to overcome T-cell dysfunction, and incorporating cutting-edge new technologies, such as gene-editing to further improve antitumor T-cell functions and reduce therapy-related toxicity. KEY MESSAGES: Advances made in ACT trials have move the field of immunotherapy for refractory solid cancers to a new stage, by constantly incorporating new strategies to develop next-generation therapies designed to enhance efficacy and improve safety and to allow a broaden access to a large numbers of patients.
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