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:State of the art and perspectives of chimeric antigen receptor T cells cell therapy for neuroblastoma.
State of the art and perspectives of chimeric antigen receptor T cells cell therapy for neuroblastoma.
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神经母细胞瘤(NB)是一种实体性神经内分泌儿童肿瘤,临床表现差异很大。高危疾病患者即使接受复杂的多模式治疗,预后仍较差,因此需要寻找新的治疗方法。CAR-T 细胞显著改善了癌症患者的生存,尤其是血液系统恶性肿瘤患者。针对 NB 的 CAR-T 早期临床试验证明该疗法安全可行,但临床疗效有限。同时,多项实验和临床前研究表明,临床试验中最常见的单一第二代或第三代 CAR 结构不足以使实体瘤完全缓解。本文回顾工程化受体方面的最新进展及未来展望,包括可结合多种抗原的受体、第四代和第五代“装甲型”CAR-T,以及 CAR-T 与其他免疫疗法的联合策略。我们还总结 NB CAR-T 疗法正在进行的临床试验结果和局限。
Neuroblastoma (NB) is a solid, neuroendocrine pediatric solid tumor with divergent clinical behavior. Patients with high-risk diseases have poor prognoses despite complex multimodal therapy, which requires the search for new therapeutic approaches. Chimeric antigen receptor T cells (CAR-T) have led to dramatic improvements in the survival of cancer patients, most notably those with hematologic malignancies.
Early-phase clinical trials of CAR-T cell therapy for NB have proven safe and feasible, but limited clinical efficacy. At the same time, multiple experimental and preclinical studies have shown that the most common in clinical trials single 2nd or 3rd generation CAR structure is not sufficient for a complete response in solid tumors.
Here, we review the recent advances and future perspectives associated with engineered receptors, including several antigens binding, armored CAR-T of 4th and 5th generation and CAR-T cell combination strategies with other immunotherapy.
We also summarize the results and shortcomings of ongoing clinical trials of CAR-T therapy for NB.
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