纤连蛋白CH296刺激的T细胞疗法在晚期癌症患者中的I期临床试验。
Phase I clinical trial of fibronectin CH296-stimulated T cell therapy in patients with advanced cancer.
作者信息
Ishikawa Takeshi, Kokura Satoshi, Enoki Tatsuji, Sakamoto Naoyuki, Okayama Tetsuya, Ideno Mitsuko, Mineno Junichi, Uno Kazuko, Yoshida Naohisa, Kamada Kazuhiro, Katada Kazuhiro, Uchiyama Kazuhiko, Handa Osamu, Takagi Tomohisa, Konishi Hideyuki, Yagi Nobuaki, Naito Yuji, Itoh Yoshito, Yoshikawa Toshikazu
机构信息
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan ; Department of Cancer ImmunoCell Regulation, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Center for Cell and Gene Therapy, Takara Bio Inc, Otsu, Japan.
出版信息
PLoS One. 2014 Jan 31;9(1):e83786. doi: 10.1371/journal.pone.0083786. eCollection 2014.
BACKGROUND
Previous studies have demonstrated that less-differentiated T cells are ideal for adoptive T cell transfer therapy (ACT) and that fibronectin CH296 (FN-CH296) together with anti-CD3 resulted in cultured cells that contain higher amounts of less-differentiated T cells. In this phase I clinical trial, we build on these prior results by assessing the safety and efficacy of FN-CH296 stimulated T cell therapy in patients with advanced cancer.
METHODS
Patients underwent fibronectin CH296-stimulated T cell therapy up to six times every two weeks and the safety and antitumor activity of the ACT were assessed. In order to determine immune function, whole blood cytokine levels and the number of peripheral regulatory T cells were analyzed prior to ACT and during the follow up.
RESULTS
Transferred cells contained numerous less-differentiated T cells greatly represented by CD27+CD45RA+ or CD28+CD45RA+ cell, which accounted for approximately 65% and 70% of the total, respectively. No ACT related severe or unexpected toxicities were observed. The response rate among patients was 22.2% and the disease control rate was 66.7%.
CONCLUSIONS
The results obtained in this phase I trial, indicate that FN-CH296 stimulated T cell therapy was very well tolerated with a level of efficacy that is quite promising. We also surmise that expanding T cell using CH296 is a method that can be applied to other T- cell-based therapies.
TRIAL REGISTRATION
UMIN UMIN000001835.
背景
先前的研究表明，分化程度较低的T细胞是过继性T细胞转移疗法（ACT）的理想选择，并且纤连蛋白CH296（FN-CH296）与抗CD3共同作用可使培养的细胞中含有更多分化程度较低的T细胞。在这项I期临床试验中，我们基于这些先前的结果，评估了FN-CH296刺激的T细胞疗法在晚期癌症患者中的安全性和疗效。
方法
患者每两周接受多达六次纤连蛋白CH296刺激的T细胞疗法，并评估ACT的安全性和抗肿瘤活性。为了确定免疫功能，在ACT之前和随访期间分析全血细胞因子水平和外周调节性T细胞的数量。
结果
转移的细胞包含大量分化程度较低的T细胞，以CD27 + CD45RA +或CD28 + CD45RA +细胞为主，分别占总数的约65％和70％。未观察到与ACT相关的严重或意外毒性。患者的缓解率为22.2％，疾病控制率为66.7％。
结论
该I期试验获得的结果表明，FN-CH296刺激的T细胞疗法耐受性良好，疗效很有前景。我们还推测，使用CH296扩增T细胞是一种可应用于其他基于T细胞的疗法的方法。
试验注册
UMIN UMIN000001835。
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