肿瘤细胞治疗研究
英文原题：Dual-Targeting CAR-NK Cells for Recurrent Ovarian Cancer (MSLN, FRα, MUC16)
这是一项 I/II 期注册临床试验，评估 NK 细胞治疗卵巢癌、急性淋巴细胞白血病的安全性、可行性及初步疗效。当前状态：招募中。计划入组 36 例。试验地点：中国 · 深圳（共 1 个中心，其中中国 1 个）。登记号：NCT07480954。
仅女性 · ≥ 18 Years 且 ≤ 75 Years
纳入标准： • 组织学确诊为上皮性卵巢癌、输卵管癌或原发性腹膜癌（优先高等级浆液性癌）。 • 至少接受过2线全身治疗后疾病复发或难治（除非有禁忌证，治疗中应包括含铂方案）。 • 根据RECIST 1.1有可测量病灶。 • 肿瘤表达以下靶点中至少2种且超过方案规定阈值：MSLN、FRα（FOLR1）、MUC16（CA125）；可使用存档或新鲜活检样本。 • ECOG体能状态评分0～1分。 • 器官功能充足，例如：ANC≥1.0×10⁹/L；血小板≥75×10⁹/L；血红蛋白≥8 g/dL；AST/ALT≤ULN的3倍（肝转移者≤ULN的5倍）；总胆红素≤ULN的1.5倍；肌酐清除率≥50 mL/min。 • 有生育能力的女性妊娠试验阴性；同意在输注后12个月内（或按当地基因治疗指南规定）采取有效避孕措施。 • 能遵守研究流程和随访计划，并签署书面知情同意书。 排除标准： • 过去6个月内接受过基因修饰细胞治疗（如CAR-T、CAR-NK），或既往接受过方案规定的靶向相同抗原治疗。 • 存在需要治疗的活动性中枢神经系统（CNS）转移或癌性脑膜炎。 • 存在未控制的感染（包括活动性结核）或有临床意义的未控制病毒感染。 • 已知HIV感染且病毒血症未控制；活动性乙肝或丙肝且病毒载量可检测（筛选时须检测）。 • 存在有临床意义的心血管疾病（如近期心肌梗死、未控制心律失常或NYHA Ⅲ／Ⅳ级心力衰竭）。 • 30天内患有需要全身免疫抑制治疗的活动性自身免疫性疾病（允许生理性激素替代）。 • 在方案规定的洗脱期内接受不允许的其他抗癌治疗（化疗、靶向治疗或放疗）。 • 淋巴细胞清除前4周内接受过重大手术（小型操作除外）。
Inclusion Criteria: * Histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma (high-grade serous preferred). * Recurrent or refractory disease after at least 2 prior systemic treatment lines (including a platinum-based regimen unless contraindicated). * Measurable disease per RECIST v1.1. * Tumor expresses at least two of the following targets above protocol-defined threshold: MSLN, FRalpha (FOLR1), MUC16 (CA 125) (archival or fresh biopsy). * ECOG performance status 0-1. * Adequate organ function (example): ANC \>= 1.0 x 10\^9/L; platelets \>= 75 x 10\^9/L; hemoglobin \>= 8 g/dL; AST/ALT \<= 3 x ULN (\<= 5 x ULN with liver metastases); total bilirubin \<= 1.5 x ULN; creatinine clearance \>= 50 mL/min. * Negative pregnancy test for women of childbearing potential; agreement to use effective contraception through 12 months post-infusion (or per local gene-therapy guidance). * Able to comply with study procedures and follow-up schedule; written informed consent. Exclusion Criteria: * Prior gene-modified cellular therapy (e.g., CAR-T, CAR-NK) within 6 months (or any prior therapy directed to the same target, per protocol). * Active central nervous system (CNS) metastases or carcinomatous meningitis requiring therapy. * Uncontrolled infection, including active tuberculosis; or clinically significant, uncontrolled viral infection. * Known HIV infection with uncontrolled viremia; active hepatitis B or hepatitis C with detectable viral load (testing required at screening). * Clinically significant cardiovascular disease (e.g., recent myocardial infarction, uncontrolled arrhythmia, NYHA Class III/IV heart failure). * Active autoimmune disease requiring systemic immunosuppression within 30 days (physiologic steroid replacement allowed). * Concurrent anti-cancer therapy (chemotherapy, targeted therapy, radiotherapy) not permitted within a protocol-defined washout period. * Major surgery within 4 weeks prior to lymphodepletion (except minor procedures).
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：Incidence of dose-limiting toxicities (DLTs) · 28 Days；Incidence and severity of treatment-emergent adverse events · Incidence and severity of treatment-emergent adverse events (TEAEs) graded by CTCAE v5.0 (including CRS and ICANS) · 12 months
次要终点：Objective response rate (ORR)；Duration of response (DOR) among responders；Progression-free survival (PFS)；Overall survival (OS)
给予识别间皮素（MSLN）和叶酸受体α（FRα/FOLR1）的双靶点CAR-NK细胞。肿瘤中MSLN和FRα均超过阈值的受试者进入本组。
给予识别间皮素（MSLN）和MUC16（CA125）的双靶点CAR-NK细胞。肿瘤中MSLN和MUC16均超过阈值的受试者进入本组。
给予识别FRα（FOLR1）和MUC16（CA125）的双靶点CAR-NK细胞。肿瘤中FRα和MUC16均超过阈值的受试者进入本组。
这项Ⅰ/Ⅱ期研究评估双靶点嵌合抗原受体自然杀伤（CAR-NK）细胞用于复发或难治性上皮性卵巢癌、原发性腹膜癌或输卵管癌患者的安全性、耐受性和初步抗肿瘤活性。筛选时评估每位受试者肿瘤中的间皮素（MSLN）、叶酸受体α（FRα/FOLR1）和MUC16（CA125）表达。受试者将接受与其肿瘤抗原谱最匹配的双靶点CAR-NK产品，以降低抗原逃逸风险。
This Phase 1/2 study evaluates the safety, tolerability, and preliminary anti-tumor activity of dual-targeting chimeric antigen receptor natural killer (CAR-NK) cells in participants with recurrent or refractory epithelial ovarian, primary peritoneal, or fallopian tube cancer. At screening, each participant's tumor is assessed for expression of Mesothelin (MSLN), Folate Receptor alpha (FRalpha/FOLR1), and MUC16 (CA 125). Participants are assigned to the dual-target CAR-NK product that best matches their tumor antigen profile to reduce the risk of antigen escape.
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