Tremtelectogene empogeditemcel

对于部分侵袭性极强的血液肿瘤，干细胞移植可能是唯一具备治愈潜力的疗法。即便如此，移植后肿瘤仍可能复发，留给医生的治疗选择十分有限。 For some of the most aggressive blood cancers, a stem cell transplant may be the only treatment with the potential to cure the disease. Even so, cancers can return after transplantation, leaving doctors with limited options. 圣路易斯华盛顿大学医学院研究人员主导的一项新临床试验表明，在移植前对供体干细胞进行基因修饰，可使后续抗肿瘤治疗更安全，并且有望提升疗效。该策略会去除供体细胞上的特定蛋白，这样靶向该蛋白的疗法就可以杀伤肿瘤，同时保护移植进来的健康细胞。 A new clinical trial led by researchers at Washington University School of Medicine in St. Louis suggests that genetically modifying donor stem cells before transplantation could make follow-up cancer treatments safer and potentially more effective. The strategy removes a specific protein from donor cells so that therapies aimed at that protein can attack cancer while sparing healthy transplanted cells. 这项研究在巴恩斯犹太医院与华盛顿大学医学中心下属的西特曼癌症中心，以及美国和加拿大另外14个研究中心开展，研究结果发表于《自然·医学》。 The study was conducted at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine, and 14 other sites in the U.S. and Canada. The results were published in Nature Medicine. 事实证明，CAR-T疗法对部分侵袭性血液肿瘤疗效显著，但在急性髓系白血病（AML）、骨髓增生异常综合征（MDS）等疾病中效果欠佳。 CAR-T therapy has proved highly effective against some aggressive blood cancers, but it has not worked as well against diseases such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). 迪佩尔西奥解释道，问题在于急性髓系白血病和骨髓增生异常综合征癌细胞表面的很多蛋白，同样存在于健康髓系细胞，包括移植所用的供体干细胞上。如果CAR-T细胞被设计成攻击这类共有蛋白，就可能在杀伤肿瘤的同时，破坏健康造血干细胞。 The problem, DiPersio explained, is that many proteins found on AML and MDS cancer cells also appear on healthy myeloid cells, including donor stem cells used in transplantation. If CAR-T cells are programmed to attack one of those shared proteins, they may destroy healthy blood stem cells along with the cancer. 敲除健康干细胞的CD33Removing CD33 From Healthy Stem Cells 该临床试验中，急性髓系白血病和骨髓增生异常综合征患者接受了经过基因修饰、敲除CD33蛋白的供体干细胞。研究目标是生成健康血细胞，使其不再受靶向CD33疗法的损伤。 In the clinical trial, patients with AML and MDS received donor stem cells that had been genetically modified to remove a protein called CD33. The goal was to create healthy blood cells that would no longer be vulnerable to treatments designed to attack CD33. “本研究结果令人鼓舞，显示敲除CD33的干细胞移植疗效与标准干细胞移植十分接近。”华盛顿大学医学中心基因与细胞免疫治疗中心主任迪佩尔西奥说，“未来，我们希望将该方案与靶向CD33的免疫疗法（如CAR-T细胞）联用，改善这类高侵袭性血液肿瘤患者的治疗选择。” "We are encouraged by the results of this study showing that a CD33-deleted stem cell transplant looks very similar to the outcomes of standard stem cell transplantation," said DiPersio, who also directs WashU Medicine's Center for Gene and Cellular Immunotherapy. "In the future, we are hopeful we will be able to combine this with CD33-targeted immunotherapies, such as CAR-T cells, and improve treatment options for patients with these very aggressive blood cancers." 迪佩尔西奥及其合作者还报道了一例高危急性髓系白血病病例：患者接受敲除CD33的干细胞移植；后续肿瘤复发后，采用由同一供体T细胞制备的靶向CD33 CAR-T细胞进行治疗。 DiPersio and his collaborators have also reported a single case involving a patient with high-risk AML who received a CD33-deleted stem cell transplant. When the cancer later returned, the patient was treated with CD33-targeted CAR-T cells made from T cells provided by the same donor who supplied the original stem cells. 该患者罹患的是恶性程度最高的一类急性髓系白血病，经CAR-T治疗后达到完全缓解，且持续无癌生存超过一年。患者造血功能恢复正常，所有血细胞均缺失CD33蛋白。这一结果说明基因改造后的供体细胞已成功在骨髓定植。迪佩尔西奥是该研究的资深作者，论文于2025年10月发表在《JCO精准肿瘤学》。 The patient, who had one of the most aggressive forms of AML, entered complete remission and remained cancer-free more than one year after CAR-T treatment. Normal blood cell production also returned, and all of the patient's blood cells lacked CD33. That finding indicated that the genetically engineered donor cells had successfully established themselves in the bone marrow. DiPersio is the senior author of that study, which was published in October 2025 in JCO Precision Oncology. CD33是该策略极具吸引力的靶点，因为该蛋白仅表达于造血细胞，其他组织不表达。证据同时表明，CD33并非造血干细胞正常功能所必需：天生缺失该蛋白的人群并未出现相关健康问题。 CD33 is an attractive target for this strategy because the protein is found only on blood-forming cells and not on other tissues. Evidence also suggests that CD33 is not necessary for normal blood stem cell function, since people born without the protein do not appear to have related health problems. 理论上，在成功移植敲除CD33干细胞后，体内仍表达CD33的细胞基本都是肿瘤细胞。此时使用靶向CD33的CAR-T疗法或其他免疫疗法，就可以杀伤癌细胞，而不伤害源自供体的健康血细胞。 After a successful transplant with CD33-deleted stem cells, the theory is that any cells still carrying CD33 should primarily be cancer cells. A CAR-T therapy or another immunotherapy targeting CD33 could then attack those cancer cells while leaving the healthy donor-derived blood cells alone. 这项1/2期多中心临床试验纳入30名复发高风险成人急性髓系白血病或骨髓增生异常综合征患者。移植前，研究团队利用CRISPR基因编辑敲除供体干细胞的CD33。 The phase 1/2 multicenter trial enrolled 30 adults with AML or MDS who were considered at high risk of relapse. Before transplantation, donor stem cells were modified with CRISPR gene editing to remove CD33. 这款敲除CD33的干细胞产品名为tremtelectogene empogeditemcel（trem-cel），由沃生物制药公司研发，该公司为本研究提供资助。 The resulting CD33-deleted stem cell product is called tremtelectogene empogeditemcel (trem-cel). It was developed by Vor Biopharma, which funded the study.测试靶向CD33抗肿瘤药物Testing a CD33-Targeted Cancer Treatment 为验证经编辑的干细胞能否耐受靶向CD33的治疗，患者在移植后还接受了维持治疗。 To test whether the edited stem cells could withstand a therapy directed at CD33, patients also received a maintenance treatment after transplantation. 该药物为吉妥珠单抗奥唑米星，并非靶向CD33的CAR-T疗法，而是一种工程化抗体，能够识别CD33，并将抗肿瘤药物直接递送至表达该蛋白的细胞。 The drug, gemtuzumab ozogamicin, is not a CD33-targeted CAR-T therapy. Instead, it is an engineered antibody that recognizes CD33 and delivers an anti-cancer drug directly to cells carrying the protein. 吉妥珠单抗奥唑米星已获美国食品药品监督管理局批准用于CD33阳性急性髓系白血病，目前正在开展临床试验评估其治疗CD33阳性骨髓增生异常综合征的效果。虽然该药物有助于预防复发，但毒副作用限制了它的应用，包括肝毒性以及健康血细胞损伤，患者可能出现白细胞、红细胞和血小板严重降低。 Gemtuzumab ozogamicin is approved by the Food and Drug Administration for CD33-positive AML and is being tested in clinical trials for CD33-positive MDS. Although the treatment can help prevent relapse, its usefulness is limited by side effects that include liver toxicity and damage to healthy blood cells. Patients can develop dangerously low levels of white blood cells, red blood cells and platelets.基因编辑细胞成功植活Gene-Edited Cells Successfully Engrafted 30名患者全部在第28天实现细胞植活，即移植干细胞成功到达骨髓并开始生成血细胞。部分患者植活时间更早，血小板生成平均在第16天恢复。 All 30 patients achieved engraftment by day 28, meaning the transplanted stem cells reached the bone marrow and began producing blood cells. Some patients reached that milestone sooner, while platelet production returned by day 16, on average. 上述恢复时间与标准干细胞移植的常规表现相近。 Those recovery times were similar to what is typically seen with standard stem cell transplantation. 本试验患者中位总生存期略超14个月。共有19名患者按照剂量递增方案接受至少一个周期吉妥珠单抗奥唑米星治疗，帮助研究者确定推荐给药剂量。 Average survival in the trial was just over 14 months. Nineteen patients received at least one cycle of gemtuzumab ozogamicin as part of a dose-escalation protocol, allowing researchers to identify a recommended dose. 在不同给药剂量下，患者血细胞计数均可维持稳定。该结果提示，经过基因编辑的移植细胞保护患者免于出现常规干细胞移植后使用该维持治疗时常发生的严重血细胞下降。 Across the different doses, patients maintained their blood cell counts. The finding suggests that the gene-edited transplant protected them from the severe drops in blood cells that often occur when this maintenance therapy is used after a conventional stem cell transplant.不良反应与标准移植相近Side Effects Remained Similar to Standard Transplants 治疗期间观察到的不良反应总体与标准干细胞移植相关不良反应类似，包括贫血、血小板减少、发热、感染以及移植物抗宿主病（供体细胞攻击患者自身健康组织）。 The side effects seen during treatment were broadly similar to those associated with standard stem cell transplantation. They included anemia, low platelet counts, fever, infections and graft-versus-host disease, in which donor cells attack the patient's healthy tissues. 研究期间共有7例患者死亡，其中4例死于肿瘤进展，3例与移植相关并发症有关，包括肾衰竭、肝毒性与脓毒症。 Seven patients died during the study. Four deaths resulted from progression of the cancer, while three were linked to transplant-related complications, including kidney failure, liver toxicity and sepsis. 迪佩尔西奥表示，该研究结果为后续疗法奠定基础，可将敲除CD33干细胞移植与靶向CD33免疫疗法联用。其目标是让医生能够更强效地杀伤癌细胞，同时不会破坏重建患者造血系统所需的健康供体细胞。 DiPersio said the findings provide a foundation for future treatments that pair CD33-deleted stem cell transplantation with CD33-targeted immunotherapies. The goal is to allow doctors to attack cancer cells more aggressively without simultaneously destroying the healthy donor cells needed to rebuild the patient's blood system. Journal References: CRISPR−Cas9 CD33-deleted allogeneic hematopoietic cell transplantation with gemtuzumab ozogamicin maintenance in AML: a phase 1/2 trial. Nature Medicine, 2026; 32 (5): 1763 DOI: 10.1038/s41591-026-04362-1 Remission of TP53 -Mutant AML After Transplantation With Trem-Cel, a CRISPR/Cas9 Gene-Edited Allograft Lacking CD33, Followed by a Donor-Derived Anti-CD33 Chimeric Antigen Receptor T (VCAR33). JCO Precision Oncology, 2025; (9) DOI: 10.1200/PO-25-00556 补充：tremtelectogene empogeditemcel的命名 这是WHO INN 国际通用名 + USAN 美国采用名的基因修饰细胞治疗药物双词命名体系，不是普通英文自然词，是药监标准化人造词，遵循：第一词描述基因操作；第二词描述细胞来源/ 类型。 ① tremtelectogene（第一个词，基因编辑部分） trem-telecto-gene 1.trem-：产品缩写源头trem-cel的自定义前缀（取自早期代号VOR33，厂商指定唯一标识） 2.telecto-：electroporation（电穿孔，CRISPR 体外电转导入 gRNA/Cas9）的改造嵌入词干：electo → telecto，代表电穿孔基因编辑 3.-gene：INN 标准后缀，代表基因修饰（gene component） tremtelectogene = “经电穿孔 CRISPR 编辑的基因修饰组分” ② empogeditemcel（第二个词，细胞组分） empo-gedit-em-cel 1.empo-：异基因，供者来源，非患者自体 2.gedit-：gene edit（基因编辑）的缩写嵌入词干，代表基因敲除 3.-em-：hematopoietic（造血的）词干片段 4.-cel：INN/USAN 强制后缀 = cellular product，细胞制品 empogeditemcel = 异基因、经基因编辑的造血干细胞产品 一句话构词逻辑 tremtelectogene empogeditemcel = 【trem 标识 + 电穿孔编辑 + 基因修饰】【异基因 + 基因编辑 + 造血 + 细胞制剂】中文理解：经电穿孔CRISPR 敲除 CD33 的异基因造血干细胞产品