Chimeric antigen receptor T-cell immunotherapy in breast cancer: development and challenges.

Chimeric antigen receptor T-cell immunotherapy in breast cancer: development and challenges.
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DOI:
10.7150/jca.54095
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发表时间:
2021
期刊:
影响因子:
3.9
通讯作者:
Shi Y
Shi Y
中科院分区:
医学3区
文献类型:
--
作者:
Toulouie S;Johanning G;Shi Y

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嵌合抗原受体 (CAR) T 细胞疗法是一种创新形式的免疫疗法,其中自体 T 细胞经过基因修饰,可表达编码抗原特异性单链可变片段和共刺激分子的嵌合受体。此外,CAR T细胞疗法只能在免疫系统完整的患者中成功发挥作用。因此,接受细胞毒性化疗的患者会出现免疫抑制,从而导致 CAR-T 疗法的效果降低。在过继性 CD8+ T 细胞疗法 (ACT) 中,大量肿瘤特异性工程 T 细胞取自患者,在体外扩增,并回输表达肿瘤特异性抗原受体。最成功的 ACT 是针对 B 细胞淋巴瘤的抗 CD19 嵌合抗原受体 T 细胞疗法,已被证明是有效的。然而,目前利用这种方法治疗乳腺癌等实体瘤的努力仅显示出有限的改善。尽管如此,在免疫学进步的时代,CAR-T疗法的潜在疗效还是充满希望的。通过适当地操纵 CAR T 细胞来对抗肿瘤微环境的免疫抑制力量,可能会显着根除实体瘤。本综述讨论了 CAR T 细胞疗法及其在乳腺癌过继细胞移植中的特异性和安全性。我们将重点介绍 CAR T 细胞免疫疗法的新发现以及强大的障碍,包括抑制 T 细胞功能和肿瘤部位的定位。
Chimeric antigen receptor (CAR) T-cell therapy is an innovative form of immunotherapy wherein autologous T-cells are genetically modified to express chimeric receptors encoding an antigen-specific single-chain variable fragment and costimulatory molecules. Moreover, CAR T-cell therapy can only work successfully in patients who have an intact immune system. Therefore, patients receiving cytotoxic chemotherapy will be immunosuppressed making CAR-T therapy less effective. In adoptive CD8+ T-cell therapy (ACT), numerous tumor-specific, engineered T-cells are sourced from patients, expanded in vitro, and infused back expressing tumor-specific antigen receptors. The most successful ACT, anti-CD19 chimeric antigen receptor T-cell therapy directed against B-cell lymphoma, has proved to be efficacious. However, current efforts to utilize this approach for solid tumors, like breast cancer, have shown only modest improvement. Nevertheless, the potential efficacy of CAR-T therapy is promising in an era of immunological advances. By appropriately manipulating CAR T-cells to combat the immunosuppressive forces of the tumor microenvironment, significant eradication of the solid tumor may occur. This review discusses CAR T-cell therapy and its specificity and safety in adoptive cell transfers in breast cancer. We will highlight novel discoveries in CAR T-cell immunotherapy and the formidable barriers including suppression of T-cell function and localization at tumor sites.
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