单细胞追踪揭示黑色素瘤 TIL 治疗过程中肿瘤反应性 T 细胞的可塑性
Single-cell tracking reveals tumor-reactive T cell plasticity during melanoma TIL therapy.
TIL(肿瘤浸润淋巴细胞)过继细胞治疗可在转移性黑色素瘤中诱导持久缓解,然而在体外扩增过程中及回输后,调控肿瘤反应性T细胞命运的克隆和转录动态仍知之甚少。
英文原题:Eradicating tumor in a recurrent cervical cancer patient with autologous tumor-infiltrating lymphocytes and a modified lymphodepleting regimen.
Eradicating tumor in a recurrent cervical cancer patient with autologous tumor-infiltrating lymphocytes and a modified lymphodepleting regimen.
她在一次性 TILs 输注后 10 周达到完全缓解。
TIL(肿瘤浸润淋巴细胞)疗法在多种癌症中显示出良好的治疗效果。然而,传统的淋巴细胞清除方案较为严重,是TIL更广泛应用的主要限制。改良的预处理策略可能减轻副作用,并证明肿瘤反应性T细胞在血液中的持续存在。在此,我们报告一例被诊断为复发性宫颈癌伴膀胱转移的患者。在省略高剂量IL-2的情况下,她在接受TIL静脉输注前约48小时,接受了环磷酰胺(20 mg/kg)静脉给药,持续3天。给予半剂量(100 mg)PD1抗体,目的是中和T细胞表面表达的PD1。她在一次性TIL输注后10周达到完全缓解。不良反应可忽略不计,并且可在普通病房安全处理,无需重症监护病房干预。时序外周血计数和TCR repertoire测序显示,输注的TIL发生了强劲扩增并长期持续存在。这些结果说明了改良淋巴细胞清除后序贯TIL治疗局部复发性宫颈癌患者的潜在价值。试验注册号,NCT04766320。
Tumor-infiltrating lymphocyte (TIL) therapy has shown promising results against several cancers. However, traditional lymphodepleting regimens are severe and represent a major limitation for a more widespread use of TIL. The modified pretreatment strategies may alleviate side effects and demonstrate the persistence of tumor-reactive T cells in the blood. Here, we report a case who was diagnosed recurrent cervical cancer with bladder metastasis. Omitting high dose of IL-2, she received intravenous dose of cyclophosphamide (20 mg/kg) for 3 days, approximately 48 hours before receiving the intravenous infusion of TILs. Half dosage (100 mg) of PD1 antibody was administered with purpose of neutralizing PD1 expressed on T cells surface. She achieved complete response 10 weeks after one-time TILs infusion. Adverse reactions were negligible and safely manageable in a general ward without the need for intervention from intensive care units. Time-course peripheral blood counts and TCR repertoire sequencing demonstrated a robust expansion and long-term persistence of the infused TILs. These results illustrated the potential value of modified lymphodepletion, followed by TILs for the treatment of patients with cervical cancer with local recurrence. Trial registration number, NCT04766320.
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