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294 Comparison of preclinical efficacy between CD19 CAR-T and CD3×CD19 bispecific antibody (blinatumomab)
  1. Xiangnan Qiang1,
  2. Ronghua Zhang2,
  3. Zhixiang Zhang2,
  4. Chenhui He3,
  5. Zhifeng Zhao3,
  6. Jingwei Huang2,
  7. Ting Ni4,
  8. Jun Huang4 and
  9. Xiangyi Wang2
  1. 1WuXi AppTec, Cambridge, MA, USA
  2. 2Wuxi App Tec, Shanghai, China
  3. 3 WuXi AppTec, Nantong, Jiangsu, China
  4. 4WuXi AppTec, Suzhou, Jiangsu, China
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background Bispecific antibodies and CAR-T have been increasingly involved in cancer therapy, especially in treating hematologic tumors, where both treatments demonstrate impressive therapeutic effect in patients with B-cell lymphomas and leukemia. However, limited research were available for comparison between the two types of therapies. Here we describe a comparison in preclinical efficacy between bispecific antibodies and CAR-T, through the demonstration of both in vitro and in vivo efficacy evaluations of CD19 CAR-T (FMC63–41BB-CD3Z) and CD3×CD19 bispecific antibodies (Blinatumomab).

Methods To evaluate in vitro cytotoxicity, CFSE-labelled CD19 positive Raji cells were co-cultured either with CD19 CAR-T or PBMCs supplemented with gradient concentrations of Blinatumomab. The level of apoptosis in Raji cells after co-culture was analyzed using flow cytometry at 4 to 48 hours. To evaluate in vivo tumor suppression, Raji tumor-bearing mice were grouped into CD19 CAR-T or Blinatumomab groups with separate conduct: In the CD19 CAR-T group, mice were administered with CAR-T through intravenous injection (1million CAR-T/mouse). In the Blinatumomab group, hPBMCs transplant were performed, and mice were administered with Blinatumomab six times via intravenous injection (0.5 μg/mouse). Tumor volume were monitored on weekly basis, peripheral blood were analyzed for CAR-T pharmacokinetics study.

Results For in vitro cytotoxicity, CD19 CAR-T exhibited complete cytotoxicity towards Raji tumor cells in 24 hours at effector-target ratio of 1, while Blinatumomab demonstrated complete cytotoxicity towards Raji tumor cells in 48 hours at concentration of 1ng/mL. For in vivo tumor suppression, CD19 CAR-T showed complete response rate of 100% (6/6) 7 days after administration and no relapse event in later 39 days. CAR-T were detectable until day 21, no significant body weight changes were observed. Blinatumomab showed complete response rate of 100% (6/6) 7 days after administration and the relapse rate was 66.7% (4/6) at 14 days after administration.

Conclusions Both CD19 CAR-T and Blinatumomab demonstrated a similar in vitro tumor suppressive effect and an initial in vivo response rate. However, CAR-T showcased a greater advantage in maintaining remission due to their more sustained pharmacokinetics and better in vivo proliferation capacity.

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