Treatment options for ovarian cancer patients are limited, and a high unmet clinical need remains for targeted and long-lasting, efficient drugs. Genetically modified T cells expressing chimeric antigen receptors (CAR), are promising new drugs that can be directed towards a defined target and have shown efficient, as well as persisting, anti-tumor responses in many patients. We sought to develop novel CAR T cells targeting ovarian cancer and to assess these candidates preclinically. First, we identified potential CAR targets on ovarian cancer samples. We confirmed high and consistent expressions of the tumor-associated antigen FOLR1 on primary ovarian cancer samples. Subsequently, we designed a series of CAR T cell candidates against the identified target and demonstrated their functionality against ovarian cancer cell lines in vitro and in an in vivo xenograft model. Finally, we performed additional in vitro assays recapitulating immune suppressive mechanisms present in solid tumors and developed a process for the automated manufacturing of our CAR T cell candidate. These findings demonstrate the feasibility of anti-FOLR1 CAR T cells for ovarian cancer and potentially other FOLR1-expressing tumors.
卵巢癌患者的治疗选择有限，临床上仍迫切需要靶向性强、作用持久且高效的新型药物。表达嵌合抗原受体（CAR）的基因修饰T细胞作为前景广阔的新型疗法，能够特异性识别既定靶点，并在众多患者中展现出持续有效的抗肿瘤应答。本研究致力于开发靶向卵巢癌的新型CAR T细胞，并开展临床前评估。首先，我们在卵巢癌样本中筛选出潜在的CAR靶点，证实肿瘤相关抗原FOLR1在原代卵巢癌样本中呈现高水平稳定表达。随后，我们针对该靶点设计了一系列候选CAR T细胞，通过体外实验及体内异种移植模型验证其对卵巢癌细胞系的功能活性。最后，我们通过模拟实体瘤免疫抑制机制的体外实验，建立了候选CAR T细胞的自动化制备工艺。这些研究结果证实了抗FOLR1 CAR T细胞治疗卵巢癌及潜在其他FOLR1阳性肿瘤的可行性。
Preclinical Evaluation of Novel Folate Receptor 1-Directed CAR T Cells for Ovarian Cancer
肿瘤(癌症)患者之家