肿瘤细胞治疗研究
英文原题：Preclinical Evidence of an Allogeneic Dual CD20xCD22 CAR to Target a Broad Spectrum of Patients with B-cell Malignancies.
Preclinical Evidence of an Allogeneic Dual CD20xCD22 CAR to Target a Broad Spectrum of Patients with B-cell Malignancies.
尽管自体嵌合抗原受体（CAR）T 细胞取得了显著成功，但部分患者仍因肿瘤抗原逃逸以及抗原表达低或不均等机制而复发。
尽管自体嵌合抗原受体（CAR）T细胞取得显著成功，部分患者仍因肿瘤抗原逃逸、抗原表达低或不均一等机制而复发。复发后的治疗选择有限，凸显优化现有方法的必要性。此外，还需开发来自健康供者、可在治疗决策时随时使用的异基因“现货型”疗法，以克服现有自体疗法的局限。为同时应对这两项挑战，研究人员构建了CD20×CD22双靶点异基因CAR-T细胞。本研究显示，异基因CD20×CD22 CAR-T细胞在体外和体内均具有强效、持久且呈剂量依赖性的活性，并能有效靶向CD22和CD20表达水平不一的原代B细胞非霍奇金淋巴瘤（B-NHL）样本。总体而言，本研究提供了临床前概念验证数据，支持通过双靶点异基因CAR-T克服B-NHL CAR-T治疗当前的耐药机制，并为CD19靶向疗法提供潜在替代方案。
Despite the remarkable success of autologous chimeric antigen receptor (CAR) T cells, some patients relapse due to tumor antigen escape and low or uneven antigen expression, among other mechanisms. Therapeutic options after relapse are limited, emphasizing the need to optimize current approaches. In addition, there is a need to develop allogeneic "off-the-shelf" therapies from healthy donors that are readily available at the time of treatment decision and can overcome limitations of current autologous approaches. To address both challenges simultaneously, we generated a CD20xCD22 dual allogeneic CAR T cell. Herein, we demonstrate that allogeneic CD20x22 CAR T cells display robust, sustained and dose-dependent activity in vitro and in vivo, while efficiently targeting primary B-cell non-Hodgkin lymphoma (B-NHL) samples with heterogeneous levels of CD22 and CD20. Altogether, we provide preclinical proof-of-concept data for an allogeneic dual CAR T cell to overcome current mechanisms of resistance to CAR T-cell therapies in B-NHL, while providing a potential alternative to CD19 targeting.
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