肿瘤细胞治疗研究
英文原题：An Exploratory Clinical Study Evaluating the Safety and Efficacy of Allogeneic CAR-NK Cell Therapy for Metastatic Castration-resistant Prostate Cancer (mCRPC)
这是一项早期 I 期注册临床试验，评估 CAR-NK 细胞治疗前列腺癌的安全性、可行性及初步疗效。当前状态：招募中。计划入组 15 例。试验地点：中国 · 北京（共 1 个中心，其中中国 1 个）。登记号：NCT07298239。
仅男性 · ≥ 18 Years
纳入标准： * ≥18岁的男性； * 确诊转移性去势抵抗性前列腺癌（mCRPC），并符合以下条件：①血清睾酮处于去势水平（<50 ng/dL或<1.7 nmol/L）；②符合以下任一项：a. PSA进展：至少间隔1周进行的连续3次PSA升高，其中2次较PSA最低值升高≥50%，且PSA>2 ng/mL；b. 影像学进展：骨扫描发现≥2个新病灶，或按实体瘤疗效评价标准（RECIST）评估的软组织病灶增加； * 预期生存期≥6个月； * ECOG体能状态评分0–2分； * 前列腺特异性膜抗原（PSMA）表达阳性； * 自愿参加、提供书面知情同意并能够遵守随访要求。 排除标准： * 既往接受过除研究产品外的其他细胞治疗，如树突状细胞（DC）、细胞因子诱导的杀伤细胞（CIK）、T细胞、NK细胞、CAR-T等； * 筛查前5年内有其他恶性肿瘤史（完全缓解的原位癌或研究者认为进展缓慢的恶性肿瘤除外）； * 主要器官功能异常：a. ANC<1.5×10⁹/L、血小板<100×10⁹/L或血红蛋白<9 g/dL；b. 肝功能：ALT和AST≥2.5×ULN（有肝转移者≥5×ULN）；c. 肾功能：血清肌酐≥1.5×ULN；d. 凝血功能：PT、APTT或INR≥1.5×ULN； * 正在治疗的活动性感染（病毒、细菌或真菌感染）；过去6周内有感染且需静脉抗生素治疗≥7天；或过去1周内有需要口服抗生素治疗的活动性感染； * 活动性自身免疫性疾病，或有需要长期免疫抑制治疗的严重自身免疫性疾病史； * 过去3个月内参加其他临床试验； * 无法采取有效避孕措施； * 对生物大分子药物有超敏反应史； * 未治疗的慢性活动性乙型肝炎、HBV DNA≥1000 copies/mL的慢性乙肝病毒携带者，或活动性丙型肝炎患者； * 研究者因其他原因判断不适合参加研究。
Inclusion Criteria: * Age ≥ 18 years, male; * Diagnosis of metastatic castration-resistant prostate cancer (mCRPC) meeting the following criteria: ① Serum testosterone at castration level: \< 50 ng/dL or \< 1.7 nmol/L; ② Meeting any one of the following conditions: a. PSA progression: Three consecutive rises in PSA measured at intervals of at least 1 week, with two increases being ≥ 50% above the PSA nadir, and a PSA value \> 2 ng/mL; b. Radiographic progression: Two or more new lesions detected on bone scan, or an increase in soft tissue lesions assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST). * Expected survival ≥ 6 months; * ECOG performance status of 0-2; * Positive prostate-specific membrane antigen (PSMA) expression; * Voluntarily participate, provide written informed consent, and be able to comply with follow-up. Exclusion Criteria: * Prior treatment with other cell therapy products besides the investigational product, such as dendritic cells (DC), cytokine-induced killer cells (CIK), T cells, natural killer cells (NK), chimeric antigen receptor T-cell immunotherapy (CAR-T), etc.; * History of other malignancies within 5 years prior to screening (except for completely resolved carcinoma in situ or malignancies deemed by the investigator to be slow-progressing); * Abnormal function of major organs: a. Absolute neutrophil count (ANC) \< 1.5 × 10⁹/L; Platelet count (Plt) \< 100 × 10⁹/L; Hemoglobin (Hb) \< 9 g/dL; b. Liver function: Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≥ 2.5 × the upper limit of normal (ULN) (or ≥ 5 × ULN for subjects with liver metastases); c. Renal function: Serum creatinine (Cr) ≥ 1.5 × ULN; d. Coagulation function: Prothrombin time (PT), Activated partial thromboplastin time (APTT), International Normalized Ratio (INR) ≥ 1.5 × ULN; * Any currently treated active (viral, bacterial, fungal) infection, or any infection within the past 6 weeks requiring intravenous antibiotics for 7 days or longer, or any active infection requiring oral antibiotics within the past week; * Active autoimmune disease, or history of severe autoimmune disease requiring long-term immunosuppressive therapy; * Participation in another clinical trial study within 3 months; * Inability to employ effective contraceptive measures; * History of hypersensitivity to biologic macromolecular drugs; * Untreated chronic active hepatitis B, or chronic hepatitis B virus carriers with HBV DNA ≥ 1000 copies/mL, or patients with active hepatitis C; * Subjects deemed by the investigator to be unsuitable for participation in this study for other reasons.
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：Occurrence of treatment related adverse events as assessed by CTCAE v5.0 · Defined as \>= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment · Baseline to 1 year post infusion
次要终点：The pharmacokinetic analysis of Anti-PSMA CAR-NK Cell；The pharmacodynamics analysis of Anti-PSMA CAR NK Cell；The proportion of patients with a decrease in PSA levels from baseline；Progression-free survival (PFS) after Anti-PSMA CAR NK Cell infusion；Time to clinical progression
本研究提出一种治疗转移性去势抵抗性前列腺癌的新方法。该疾病目前仍难以控制：前列腺癌是全球男性第二常见癌症，许多患者虽接受激素治疗、新型激素药物或化疗，最终仍会进展至晚期耐药阶段。此类患者预后较差，常有骨转移等并发症，生活质量也受到显著影响，因此亟需新的治疗选择。本研究聚焦一种创新免疫疗法：经工程改造的异基因抗PSMA CAR-NK细胞可特异识别并杀伤表达前列腺特异性膜抗原（PSMA）的前列腺癌细胞。CAR-NK细胞结合了NK细胞天然的肿瘤杀伤能力及增强的靶向性，并可能减少免疫逃逸，提供潜在更安全、有效的治疗策略。本临床研究将评估抗PSMA CAR-NK细胞治疗的安全性、耐受性和初步疗效，为晚期前列腺癌患者拓展未来治疗选择。
This study introduces a new treatment approach for metastatic castration-resistant prostate cancer, a stage of disease that remains difficult to manage with current therapies. Prostate cancer is the second most common cancer in men worldwide, and many patients eventually progress to an advanced, treatment-resistant stage despite hormone therapy, newer hormonal agents, or chemotherapy. Patients with metastatic castration-resistant disease often face a poor prognosis, complications such as bone metastases, and significant impacts on quality of life, highlighting the urgent need for new treatment options. This research focuses on an innovative immunotherapy using allogeneic anti-PSMA CAR-NK cells, which are engineered natural killer cells designed to precisely recognize and kill prostate cancer cells expressing the prostate-specific membrane antigen. CAR-NK cells combine the natural tumor-killing ability of NK cells with enhanced targeting and reduced immune escape, offering a potentially safer and more effective strategy. Through this clinical study, the safety, tolerability, and preliminary effectiveness of anti-PSMA CAR-NK cell therapy will be evaluated, aiming to provide new evidence and expand future treatment possibilities for patients with advanced prostate cancer.
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