肿瘤细胞治疗研究
英文原题：Dual-Targeting CAR-NK Cells for Recurrent Ovarian Cancer (MSLN, FRα, MUC16) pt2
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：NCT07617753。
仅女性 · ≥ 18 Years 且 ≤ 75 Years
纳入标准：组织学确诊上皮性卵巢癌、输卵管癌或原发性腹膜癌（优先高级别浆液性癌）；至少两线全身治疗后复发/难治（除有禁忌外须包括含铂方案）；按RECIST v1.1有可测量病灶；肿瘤至少表达MSLN、FRα/FOLR1、MUC16/CA125中的两种且达到方案阈值（存档或新鲜组织均可）；ECOG 0–1；器官功能充分（ANC≥1.0×10⁹/L、血小板≥75×10⁹/L、血红蛋白≥8 g/dL、AST/ALT≤ULN的3倍，肝转移时≤5倍、总胆红素≤ULN的1.5倍、肌酐清除率≥50 mL/min）；有生育能力女性妊娠试验阴性，并同意输注后12个月内（或按当地基因治疗指南）有效避孕；能遵守研究流程和随访并签署书面知情同意。 排除标准：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相同靶点治疗；活动性CNS转移或需治疗的癌性脑膜炎；未控制感染（包括活动性结核）或具有临床意义的未控制病毒感染；HIV感染且病毒血症未控制，或活动性乙肝/丙肝且病毒可检出；有临床意义的心血管疾病（如近期心梗、未控制心律失常、NYHA III/IV级心衰）；30天内需全身免疫抑制治疗的活动性自身免疫病（生理性激素替代除外）；方案洗脱期内接受不允许的抗癌治疗；淋巴细胞清除前4周内接受重大手术（小型操作除外）；妊娠或哺乳；或研究者认为会增加风险（如严重肺病）或妨碍结果解释的其他情况。
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 : 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) * Pregnant or breastfeeding. * Any condition that, in the investigator's judgment, would increase risk (e.g., severe pulmonary disease) or interfere with study interpretation.
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 (TEAEs) graded by CTCAE v5.0 · 12 months
次要终点：Objective response rate (ORR) by RECIST v1.1；Duration of response (DOR) among responders
识别MSLN和FRα/FOLR1的双靶点CAR-NK细胞，分配给肿瘤中MSLN、FRα均超过阈值者。
识别MSLN和MUC16/CA125的双靶点CAR-NK细胞，分配给肿瘤中MSLN、MUC16均超过阈值者。
识别FRα/FOLR1和MUC16/CA125的双靶点CAR-NK细胞，分配给肿瘤中FRα、MUC16均超过阈值者。
本Ⅰ/Ⅱ期研究评估双靶点嵌合抗原受体自然杀伤（CAR-NK）细胞治疗复发或难治性上皮性卵巢癌、原发性腹膜癌或输卵管癌的安全性、耐受性和初步抗肿瘤活性。筛查时检测肿瘤间皮素（MSLN）、叶酸受体α（FRα/FOLR1）和MUC16（CA125），并根据肿瘤抗原表达谱分配最匹配的双靶点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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