Development of fully-human anti-CD30 chimeric antigen receptors

我们设计了4种不同的单链抗体分子作为抗CD30CARS的抗原识别结构域，并与这些不同的单链抗体进行了体外比较。我们选择了最佳的单链抗体，并在不同的汽车设计体外和小鼠肿瘤模型中进行了测试。我们已经确定了一种最优的scFv和汽车设计，以供进一步开发。这项工作导致了两种在小鼠身上都非常有效的汽车。我们已经选择了其中一辆车进行I期临床试验。同时完成的工作导致了编码这种汽车的临床级慢病毒载体的产生。我们已经完成了用于全人抗CD30汽车临床试验的临床方案的工作，该方案已经得到NCI机构审查委员会的批准。我们继续进行临床前工作，以改进抗CD30的汽车设计和T细胞培养方法。一项表达抗CD30汽车的T细胞的临床试验计划于2016年秋季开始。

We have designed 4 different single chain Fv molecules as antigen-recognition domains for anti-CD30 CARs and compared CARs with these different scFvs in vitro. We selected the optimal scFv, and tested it in different CAR designs in vitro and in mouse tumor models. We have identified an optimal scFv and CAR design for further development. This work led to 2 CARs that are both highly effective in mice. We have selected one of these CARs for a phase I clinical trial. Simultaneous work has been completed that has led to generation of a clinical-grade lentiviral vector encoding this CAR. We have completed work on a clinical protocol for a clinical trial of the fully-human anti-CD30 CAR, and this protocol has been approved by the NCI Institutional Review Board. We continue preclinical work to improve anti-CD30 CAR design and T-cell culture methods. A clinical trial of T cells expressing an anti-CD30 CAR is planned to start in the fall of 2016.