Tel Aviv Sourasky Medical Center, 6 Weizmann St., 6423906, Tel Aviv, Israel.
Weizmann Institute of Science, Rehovot, Israel.
Cancer Immunol Immunother. 2020 Jul;69(7):1165-1175. doi: 10.1007/s00262-020-02516-9. Epub 2020 Mar 4.
Chimeric antigen receptor T cell (CAR-T) therapy is a novel approved treatment for hematological malignancies, still under development for solid tumors. Here, we use a rate equation-based mathematical model to discover regimens and schedules that maintain efficacy while potentially reducing toxicity by decreasing the amount of CAR-T infused. Tested on an in vivo murine model of spontaneous breast cancer, we show that our mathematical model accurately recapitulates in vivo tumor growth results achieved in the previous experiments. Moreover, we use the mathematical model to predict results of new therapy schedules and successfully prospectively validated these predictions in the in vivo. We conclude that using one tenth and even one percent of a full CAR-T dose used in preclinical trials can achieve efficacious results similar to full dose treatment.
嵌合抗原受体 T 细胞(CAR-T)疗法是一种新型的血液恶性肿瘤治疗方法,目前正在开发用于实体瘤。在这里,我们使用基于速率方程的数学模型来发现方案和时间表,通过减少输注的 CAR-T 量来保持疗效,同时降低毒性。在自发性乳腺癌的体内小鼠模型上进行测试,我们表明我们的数学模型准确地再现了以前实验中体内肿瘤生长结果。此外,我们使用数学模型预测新治疗方案的结果,并成功地在体内前瞻性验证了这些预测。我们得出结论,使用临床前试验中全剂量 CAR-T 的十分之一甚至百分之一可以达到与全剂量治疗相似的有效结果。
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