肿瘤细胞治疗研究
英文原题：Clinical Study of a Novel Humanized CD70-Targeted CAR-T Cell Incorporating TLR2 for Advanced Renal Cell Carcinoma Therapy
⚠ 该试验的登记信息已有 14 个月未更新， 页面上显示的「尚未开始招募」可能已经失效。联系研究中心之前，建议先到 ClinicalTrials.gov 核对登记原文的最新状态与联系方式。
这是一项早期 I 期注册临床试验，评估 CAR-T 细胞治疗肾细胞癌的安全性、可行性及初步疗效。当前状态：尚未开始招募。计划入组 30 例。登记号：NCT07113977。
不限性别 · ≥ 18 Years 且 ≤ 75 Years
纳入标准： * 1. 患者或法定授权代表自愿参加并签署书面知情同意书； * 2. 签署知情同意书时年龄18-75岁（含），性别不限； * 3. 晚期肾细胞癌（RCC），无治愈性治疗选择，既往接受过≥1线治疗，且符合以下一项或多项： 1. 一线或后线治疗后复发。 2. 既往治疗后进展或持续进展； * 4. 经组织病理学确诊的晚期RCC，符合WHO 2016分类，至少有1个可经CT或MRI评估的可测量病灶； * 5. 经免疫组织化学（IHC）证实肿瘤组织中CD70阳性； * 6. 器官功能充分：肝功能：ALT/AST <3× ULN且总胆红素≤34.2 μmol/L。肾功能：肌酐清除率（Cockcroft-Gault）≥60 mL/min。肺功能：血氧饱和度≥95%且无活动性肺部感染。心功能：LVEF ≥50%，无显著心包积液，无临床相关心电图异常； * 7. 避孕：有生育能力的女性在筛选时妊娠试验（尿/血清）必须为阴性，并同意在输注后≥1年内使用有效避孕措施。 有生育能力伴侣的男性必须在输注后≥1年内使用屏障避孕； * 8. 体能状态：ECOG评分0-3； * 9. 预期生存期>3个月； * 10. 愿意遵守白细胞分离术、医学评估和随访访视。 排除标准： * 1. 妊娠或哺乳期女性； * 2. 未控制的真菌、细菌、梅毒螺旋体、病毒或其他感染； * 3. 活动性肝炎：HBV DNA >500 IU/mL。HCV RNA阳性（经重复检测确认）； * 4. HIV感染、已知获得性免疫缺陷综合征（AIDS）或梅毒感染； * 5. 既往接受过任何形式的基因治疗； * 6. 对生物制品（包括抗生素）、抗体、细胞因子或其他大分子药物有严重过敏反应史； * 7. 临床显著的中枢神经系统疾病：癫痫、瘫痪、失语、卒中、严重创伤性脑损伤、痴呆、帕金森病、小脑疾病、器质性脑综合征； * 8. 未控制的精神疾病； * 9. 物质滥用/成瘾； * 10. 禁用药物/治疗：皮质类固醇：白细胞分离术前2周内使用≥2 mg/kg泼尼松（或等效剂量>20 mg/天）。 化疗/放疗：白细胞分离术前3周内接受抗肿瘤放疗或挽救性化疗。 免疫抑制剂：白细胞分离术前4周内使用。其他试验/大手术：白细胞分离术前4周内参加其他临床试验或接受重大非诊断性手术。 特定药物：白细胞分离术前6个月内使用阿仑单抗，或3个月内使用氯法拉滨/克拉屈滨。
Inclusion Criteria: * 1\. Voluntary participation with written informed consent provided by the patient or legally authorized representative; * 2.Age 18-75 years (inclusive) at the time of consent, regardless of sex; * 3.Advanced-stage renal cell carcinoma (RCC) with no curative treatment options, who have received ≥1 prior line of therapy and meet one or more of the following: 1. Recurrence after first-line or later-line treatment(s). 2. Progression or persistent progression following prior therapy; * 4.Histopathologically confirmed advanced RCC per WHO 2016 classification, with at least one measurable lesion evaluable by CT or MRI; * 5.CD70 positivity in tumor tissue confirmed by immunohistochemistry (IHC); * 6.Adequate organ function: Hepatic: ALT/AST \<3× ULN and total bilirubin ≤34.2 μmol/L. Renal: Creatinine clearance (Cockcroft-Gault) ≥60 mL/min. Pulmonary: Oxygen saturation ≥95% with no active pulmonary infection. Cardiac: LVEF ≥50%, no significant pericardial effusion, and no clinically relevant ECG abnormalities; * 7.Contraception: Women of childbearing potential must have a negative pregnancy test (urine/serum) at screening and agree to use effective contraception for ≥1 year post-infusion. Men with partners of childbearing potential must use barrier contraception for ≥1 year post-infusion; * 8.Performance status: ECOG score 0-3; * 9.Life expectancy \>3 months; * 10.Willingness to comply with leukapheresis, medical assessments, and follow-up visits. Exclusion Criteria: * 1.Pregnant or lactating women; * 2.Uncontrolled fungal, bacterial, Treponema pallidum, viral, or other infections; * 3.Active hepatitis: HBV DNA \>500 IU/mL. Positive HCV RNA (confirmed by repeat testing); * 4.HIV infection, known acquired immunodeficiency syndrome (AIDS), or syphilis infection; * 5.Prior gene therapy of any form; * 6.History of severe allergic reactions to biologics (including antibiotics), antibodies, cytokines, or other macromolecular agents; * 7.Clinically significant CNS disorders: epilepsy, paresis, aphasia, stroke, severe traumatic brain injury, dementia, Parkinson's disease, cerebellar disorders, organic brain syndrome; * 8.Uncontrolled psychiatric illness; * 9.Substance abuse/addiction; * 10.Prohibited medications/treatments: Corticosteroids: ≥2 mg/kg prednisone (or equivalent \>20 mg/day) within 2 weeks before leukapheresis. Chemo/radiotherapy: Anti-tumor radiotherapy or salvage chemotherapy within 3 weeks before leukapheresis. Immunosuppressants: Use within 4 weeks before leukapheresis. Other trials/major surgery: Participation in another clinical trial or major non-diagnostic surgery within 4 weeks before leukapheresis. Specific agents: Alemtuzumab within 6 months, or clofarabine/cladribine within 3 months before leukapheresis.
以上为辅助阅读译文。是否适合入组须由主治医生判断，最终以登记平台与研究者确认为准。
主要终点：Immune Effector Cell-Associated Neurotoxicity Syndrome（ICANS） · To assess the number and severity of ICANS after treatment according to the ASTCT criteria · in 6 months；Cytokine Release Syndrome（CRS） · To assess the number and severity of CRS after treatment according to the ASTCT criteria · in 6 months；Objective response rate (ORR) · Objective response rate (ORR) will be assessed by imaging at 1 month, 6 months, and 1 year post-CAR-T infusion. · 1 month, 6 months, and 1 year
次要终点：Progression-Free Survival（PFS）；Overall Survival（OS）；Adverse Events
在这项临床研究中，晚期肾细胞癌受试者将接受一种新型人源化CD70靶向CAR-T细胞产品，该产品整合了TLR2共刺激结构域。将从每位受试者采集外周血单个核细胞，经基因修饰以表达CAR构建体，并在体外扩增；在通过多项质量控制检测后，CAR-T细胞将按预先规定的剂量输注。输注后，将通过临床症状评估、生活质量问卷、生物标志物分析、实验室检查、影像学检查、不良事件监测和长期随访，系统评价CD70导向CAR-T细胞疗法的疗效和安全性。
In this clinical study, participants with advanced renal cell carcinoma will receive a novel humanized CD70-targeted CAR-T-cell product that incorporates the TLR2 co-stimulatory domain. Peripheral blood mononuclear cells will be collected from each subject, genetically modified to express the CAR construct, and expanded ex vivo; after passing multiple quality-control assays, the CAR-T cells will be infused at the pre-specified dose. Post-infusion, the efficacy and safety of CD70-directed CAR-T-cell therapy will be systematically evaluated using clinical symptom assessments, quality-of-life questionnaires, biomarker analyses, laboratory tests, imaging studies, adverse-event monitoring, and long-term follow-up.
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