截至2020831日,共筛选 8例成人患者,纳入6例。6例患者分别接受2个剂量水平的CTA101单次输注,其中3例患者接受了1×106 CAR+T 细胞/kg,另外3例患者接受3×106 CAR+T 细胞/kg。入组到输注等待时间不超过8天。6名患者的既往中位治疗管线数为53名患者在入组前存在高白细胞血症,1名患者存在自体T细胞计数过低。


583%)患者获得CR/CRi,且均为MRD-,其中1例患者在D60缓解状态下接受了allo-HSCT治疗。中位随访时间4.3个月,5例获得CR/CRi患者中3例患者仍维持MRD-1例患者在输注后D47 MRD+且在D74确认为CD19+CD22dim复发。截至数据截至日,最长的缓解状态已持续超过8个月。






CTA101, a CRISPR/Cas9-engineered off-the-shelf CD19/CD22 dual-targeted CAR-T cell product, was evaluated in an open-label dose-escalation phase I study, which presented  at the 62nd Annual Meeting of the American Society of Hematology (ASH) by He Huang, MD, PhD, Professor of Hematology, President of The First Affiliated Hospital, Zhejiang University School of Medicine.


As of the August 31st, 2020 data cutoff, 8 adult patients were screened, and 6 adult patients all enrolled received CTA101 infusion at two dose levels (DL1 = 1×106/kg cells, DL2 =3×106/kg cells), with less than 8 days between enrollment and infusion. The median number of prior lines of therapy was 5, and three patients had hyperleukocytosis and one had CD3+ T lymphocytopenia prior to enrollment.


Across both cohorts, 5 patients (83.3%) achieved complete response (CR) or complete response with incomplete hematologic recovery (CR/CRi). Minimal residual disease (MRD) assessment was completed in five patients with a CR/CRi response and all achieved an MRD negative status. With a median follow-up of 4.3 months, three out of the five patients who achieved CR/CRi remained MRD negative. The longest sustained remission has been observed for more than 8 months to date.


No dose limiting toxicity (DLT), graft-vs-host disease (GvHD) or Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) were observed. Cytokine release syndrome (CRS) was identified in all patients, and the majority of CRS was mild and manageable with supportive therapies. Only one patient experienced grade 3 CRS and required tocilizumab and glucocorticoids treatment. No CRISPR/Cas9 genome editing associated adverse events occurred.


“We are encouraged by CTA101’s manageable safety profile and potent anti-leukemia ability, which illustrate the potential feasibility of CRISPR/Cas9-engineered universal CAR-T,” said the PI of this study, Prof. Huang. “All patients enrolled successfully received infusions within 8 days. Three patients with leukocytosis and one patient with lymphopenia prior to enrollment, for whom autologous CAR-T therapy was not suitable, received CTA101 therapy successfully in this study. These data suggest that CTA101 may offer an alternative therapy for patients with r/r ALL. I hope more and more universal CAR-T therapies can be developed to address unmet medical needs in the future.”


“We are excited to demonstrate for the first time that a CRISPR-engineered allogeneic CAR-T therapy directed at CD19/CD22 can achieve deep clinical responses,” said Xiaohong He, PhD, CEO of Bioheng. “We believe these initial results support that we are on the right track to bring the benefits of an off-the-shelf therapy to cancer patients.”

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