Biophysical and mechanobiological considerations for T-cell-based immunotherapy.
Biophysical and mechanobiological considerations for T-cell-based immunotherapy.
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DOI：
10.1016/j.tips.2023.03.007
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发表时间：
2023-06-01
影响因子：
13.8
通讯作者：
Mak, Michael
中科院分区：
文献类型：
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作者：
Zhuang, Chuzhi;Gould, Jared E;Mak, Michael
免疫疗法调节身体的防御系统来治疗癌症。虽然这些疗法已显示出对多种类型癌症的疗效，但患者的反应率有限，并且脱靶效应可能很严重。开发免疫疗法的典型方法倾向于关注抗原靶向和分子信号传导，而忽略了生物物理学和机械生物学效应。免疫细胞和肿瘤细胞都对生物物理线索有反应，这在肿瘤微环境中很突出。最近的研究表明，机械传感-包括通过Piezo 1，粘附和Yes相关蛋白（雅普）和具有PDZ结合基序（TAZ）的转录共激活因子-影响肿瘤-免疫相互作用和免疫功效。此外，生物物理方法，如流体系统和机械活化方案可以改善工程化T细胞的可控性和制造，具有提高治疗功效和特异性的潜力。本文综述了利用免疫生物物理学和机械生物学的进展改善嵌合抗原受体（CAR）T细胞和抗程序性细胞死亡蛋白1（抗PD-1）疗法。
Immunotherapies modulate the body's defense system to treat cancer. While these therapies have shown efficacy against multiple types of cancer, patient response rates are limited, and the off-target effects can be severe. Typical approaches in developing immunotherapies tend to focus on antigen targeting and molecular signaling, while overlooking biophysical and mechanobiological effects. Immune cells and tumor cells are both responsive to biophysical cues, which are prominent in the tumor microenvironment. Recent studies have shown that mechanosensing - including through Piezo1, adhesions, and Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) - influences tumor-immune interactions and immunotherapeutic efficacy. Furthermore, biophysical methods such as fluidic systems and mechanoactivation schemes can improve the controllability and manufacturing of engineered T cells, with potential for increasing therapeutic efficacy and specificity. This review focuses on leveraging advances in immune biophysics and mechanobiology toward improving chimeric antigen receptor (CAR) T-cell and anti-programmed cell death protein 1 (anti-PD-1) therapies.