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:New nonchemotherapy treatment options for cutaneous T-cell lymphomas an update.
New nonchemotherapy treatment options for cutaneous T-cell lymphomas an update.
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对于 MF/SS 患者,鉴于其皮肤屏障受损,避免全身性免疫抑制的非化疗选择是优先考虑的方案。包括 brentuximab vedotin、lacutamab、denileukin diftitox 和 mogamulizumab 在内的靶向治疗已在注册试验中显示出活性。调节肿瘤微环境和上调肿瘤特异性免疫反应的新药已进入临床试验,包括招募免疫效应细胞的双特异性抗体、消除抑制性微环境的药物以及靶向肿瘤表位的工程化 T 细胞。检查点抑制剂可能在 MF/SS 中发挥作用,但其作用尚未明确界定,且可能诱导超进展。
蕈样肉芽肿(MF)和Sézary综合征(SS)是皮肤的T细胞淋巴瘤,临床病程迁延,患者一生中需要多线治疗。由于现有药物在皮肤、淋巴结和血液中的疗效存在差异,MF/SS的治疗较为复杂。随着对该病生物学认识的深入,已出现了疗效更佳且能改善复发/难治性疾病患者生活质量的疗法。涵盖领域:本综述将概述新型生物制剂的临床数据,包括单克隆抗体、小分子抑制剂以及CAR-T 和双特异性抗体等免疫治疗手段。
INTRODUCTION: Mycosis fungoides (MF) and S zary syndrome (SS) are T cell lymphomas of the skin with prolonged clinical course requiring multiple lines of therapy in a patient's lifetime. The treatment of MF/SS with available agents is complicated by the differential response in skin, lymph nodes, and blood. Advances in understanding the biology of the disease have led to therapies with better efficacy and improvement in quality of life for patients with relapsed and refractory disease. AREAS COVERED: This review will outline clinical data for novel biologics including monoclonal antibodies, small molecule inhibitors, and immunotherapeutic approaches such as CAR-T and bispecific antibodies.
EXPERT OPINION: Nonchemotherapy options which avoid generalized immunosuppression are a preferred consideration for patients with MF/SS, given the compromised skin integument of these patients. Targeted therapies including brentuximab vedotin, lacutamab, denileukin diftitox, and mogamulizumab have shown activity in registrational trials.
Novel agents which modulate tumor microenvironment and upregulate tumor-specific immune responses have been in clinical trials, including bispecific antibodies recruiting immune effectors, agents eradicating suppressive microenvironments, and engineered T cells targeting tumor epitopes. Checkpoint inhibitors may play a role in MF/SS but their role has not been well defined, and they may induce hyper progression.
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