决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:High affinity CD16(v/v) allogeneic NK cell therapy, AB-101, enhances antibody-mediated cytotoxicity in B-cell driven diseases.
这些发现支持 AB-101 作为一种高度可扩展、耐受性良好的免疫疗法,具有作为针对致病性 B 细胞的 ADCC 增强剂的跨适应症潜力。
异体NK细胞疗法为自身免疫性疾病的治疗提供了一种优于T细胞方法的引人注目的替代方案,其优势包括强效的效应功能、良好的安全性特征以及现货可及性。AB-101是一种脐带血来源、非基因修饰、冷冻保存的NK细胞产品,采用50L生物反应器工艺进行工业化规模生产,每批次可产出1100亿个细胞。AB-101高表达CD56和CD16,包括高亲和力158V/V变异体,可增强抗体依赖性细胞介导的细胞毒性(ADCC)。表型和功能分析证实,各良好生产规范(GMP)批次间具有一致的活化NK细胞特征。AB-101在体外与靶向B细胞的单克隆抗体(mAbs)联用时对肿瘤细胞表现出强效的ADCC活性,并且与利妥昔单抗联合用于非霍奇金淋巴瘤患者时显示出积极结果,同时AB-101上的CD16保持高表达。在自身免疫模型中,内源性NK细胞表现出细胞毒性受损,而AB-101在与抗CD20或抗CD19 mAbs配对时,对系统性红斑狼疮(SLE)和类风湿关节炎(RA)患者的B细胞表现出增强的杀伤作用,提示AB-101在自身免疫性疾病中具有治疗潜力。总体而言,这些发现支持AB-101作为一种高度可扩展、耐受性良好的免疫疗法,具有作为靶向致病性B细胞的ADCC增强剂跨适应症应用的潜力。
Allogeneic NK cell therapies offer a compelling alternative to T-cell based approaches for the treatment of autoimmune diseases, with advantages including potent effector function, a favorable safety profile, and off-the-shelf availability. AB-101 is a cord blood-derived, non-genetically modified, cryopreserved NK cell product manufactured at industrial scale using a 50L bioreactor process, yielding 110 billion cells per run. AB-101 expresses high levels of CD56 and CD16, including the high-affinity 158V/V variant, which enhances antibody-dependent cellular cytotoxicity (ADCC). Phenotypic and functional analyses confirm a consistent, activated NK cell profile across Good Manufacturing Practice (GMP) lots. AB-101 demonstrates robust ADCC activity against tumor cells in vitro in combination with B-cell targeting monoclonal antibodies (mAbs) and shows positive results when administered in combination with rituximab to patients with non-Hodgkin lymphoma, with maintenance of high CD16 expression on AB-101. In autoimmune models, endogenous NK cells exhibited impaired cytotoxicity, whereas AB-101, which demonstrated enhanced killing of B cells from patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) when paired with anti-CD20 or anti-CD19 mAbs, suggesting therapeutic potential for AB-101 in autoimmune diseases. Collectively, these findings support AB-101 as a highly scalable, well-tolerated immunotherapy with potential across indications as an ADCC-enhancer targeting pathogenic B cells.
MEMBER ACCOUNT
登录成功会直接打开下一页。