The recent FDA approval of the first CAR immunotherapy marks a watershed moment in the advancement toward a cure for cancer. CD19 CAR treatment for B cell acute lymphocytic leukemia has achieved unprecedented remission rates. However, despite success in treating previously relapsed and refractory patients, CD19 CAR faces similar challenges as traditional chemotherapy, in that malignancy can adapt and overcome treatment. The emergence of both antigen positive and negative blasts after CAR treatment represents a need to bolster current CAR approaches. Here, we report on the anti-tumor activity of a CAR T cell possessing 2 discrete scFv domains against the leukemic antigens CD19 and CD123. We determined that the resulting compound CAR (cCAR) T cell possesses consistent, potent, and directed cytotoxicity against each target antigen population both in vitro and in vivo. Our findings indicate that targeting CD19 and CD123 on B-ALL cells may be an effective strategy for augmenting the response against leukemic blasts and reducing rates of relapse.

中文翻译：

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用CD19-CD123复合汽车T细胞疗法靶向与B-ALL相关的两种抗原。

FDA最近对首个CAR免疫疗法的批准标志着癌症治疗进展的分水岭。CD19 CAR治疗B细胞急性淋巴细胞白血病已达到空前的缓解率。然而，尽管成功治疗了先前复发和难治的患者，CD19 CAR仍面临与传统化疗类似的挑战，因为恶性肿瘤可以适应和克服治疗。CAR治疗后抗原阳性和阴性母细胞的出现表明需要加强当前的CAR方法。在这里，我们报道了具有2个离散的scFv结构域的CAR T细胞对白血病抗原CD19和CD123的抗肿瘤活性。我们确定所得的复合CAR（cCAR）T细胞具有一致，有效，并针对体外和体内针对每种靶抗原群体的细胞毒性。我们的发现表明，针对B-ALL细胞靶向CD19和CD123可能是增强针对白血病母细胞的反应并降低复发率的有效策略。