CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Mathematical Modeling of Tumor and Cancer Stem Cells Treated with CAR-T Therapy and Inhibition of TGF-β.
Mathematical Modeling of Tumor and Cancer Stem Cells Treated with CAR-T Therapy and Inhibition of TGF-β.
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干细胞假说认为,存在一小群恶性细胞,即癌症干细胞,它们启动肿瘤的发生,促进其生长,甚至可能是转移的原因。传统治疗,如化疗和放疗,主要针对肿瘤细胞,而留下干细胞可能导致复发。嵌合抗原受体(CAR)T细胞疗法是一种免疫疗法,其中免疫细胞被基因修饰以对抗肿瘤细胞。传统上,CAR-T 细胞疗法用于治疗血液癌症,直到最近才在对抗实体瘤方面显示出有希望的结果。我们建立了一个常微分方程模型,允许输注经过训练的CAR-T 细胞来特异性攻击存在于实体瘤微环境中的癌症干细胞。此外,我们纳入了TGF-的影响,它抑制CAR-T 细胞,从而促进肿瘤生长。我们通过将模型与可用数据进行比较来验证模型,然后检查针对非干细胞和干细胞癌症细胞的CAR-T 细胞治疗组合以及一种降低TGF-有效性的治疗,以确定消除肿瘤的方案。
The stem cell hypothesis suggests that there is a small group of malignant cells, the cancer stem cells, that initiate the development of tumors, encourage its growth, and may even be the cause of metastases. Traditional treatments, such as chemotherapy and radiation, primarily target the tumor cells leaving the stem cells to potentially cause a recurrence.
Chimeric antigen receptor (CAR) T-cell therapy is a form of immunotherapy where the immune cells are genetically modified to fight the tumor cells. Traditionally, the CAR T-cell therapy has been used to treat blood cancers and only recently has shown promising results against solid tumors.
We create an ordinary differential equations model which allows for the infusion of trained CAR-T cells to specifically attack the cancer stem cells that are present in the solid tumor microenvironment.
Additionally, we incorporate the influence of TGF- which inhibits the CAR-T cells and thus promotes the growth of the tumor.
We verify the model by comparing it to available data and then examine combinations of CAR-T cell treatment targeting both non-stem and stem cancer cells and a treatment that reduces the effectiveness of TGF- to determine the scenarios that eliminate the tumor.
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