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预测癌症过继性细胞治疗反应的生物学和分子因素

英文原题:Biological and Molecular Factors Predicting Response to Adoptive Cell Therapies in Cancer.

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Biological and Molecular Factors Predicting Response to Adoptive Cell Therapies in Cancer.

PubMed 2022/07/11(内容时间) J Natl Cancer Inst Q1 · IF 7.7(JCR 2025)

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中文摘要

过继性细胞疗法(ACT)是癌症治疗领域的重大突破,近年来因其在部分血液系统恶性肿瘤患者中展现出持久甚至治愈性的疗效而不断扩展。ACT利用免疫系统的抗原特异性和细胞毒性机制,尤其依赖患者自身的T淋巴细胞来靶向并清除恶性细胞。这种个性化治疗策略体现了基础、转化和临床研究人员共同努力的成功,将患者的免疫系统转变为寻找癌症治愈方法的重要盟友。ACT正在不断改进,以达到最大的临床获益。尽管对于某些类型的癌症,主要是黑色素瘤和血液系统恶性肿瘤,这些疗法是非常有前景的治疗选择,但这些个体化治疗仍存在若干不足,包括费用高昂、技术挑战、不良反应的管理以及应答患者群体有限。

因此,发现和开发可靠且稳健的生物标志物,以特异且灵敏地识别最可能从ACT中获益的患者以及发生潜在严重毒性风险较高的患者,至关重要。尽管尚未确定输注细胞疗法成功的独特读数,但过继细胞、肿瘤和/或肿瘤微环境的某些特征已被认为可预测患者接受ACT的结局。

在此,我们评述生物标志物在预测ACT成功机会方面的重要性,以最大化治疗疗效并提高患者生存率。

展开英文摘要原文

Adoptive cell therapy (ACT) constitutes a major breakthrough in cancer management that has expanded in the past years due to impressive results showing durable and even curative responses for some patients with hematological malignancies. ACT leverages antigen specificity and cytotoxic mechanisms of the immune system, particularly relying on the patient's T lymphocytes to target and eliminate malignant cells.

This personalized therapeutic approach exemplifies the success of the joint effort of basic, translational, and clinical researchers that has turned the patient's immune system into a great ally in the search for a cancer cure. ACTs are constantly improving to reach a maximum beneficial clinical response.

Despite being very promising therapeutic options for certain types of cancers, mainly melanoma and hematological malignancies, these individualized treatments still present several shortcomings, including elevated costs, technical challenges, management of adverse side effects, and a limited population of responder patients.

Thus, it is crucial to discover and develop reliable and robust biomarkers to specifically and sensitively pinpoint the patients that will benefit the most from ACT as well as those at higher risk of developing potentially serious toxicities. Although unique readouts of infused cell therapy success have not yet been identified, certain characteristics from the adoptive cells, the tumor, and/or the tumor microenvironment have been recognized to predict patients' outcome on ACT.

Here, we comment on the importance of biomarkers to predict ACT chances of success to maximize efficacy of treatments and increase patients' survival.

论文信息

作者
Ferrer G、Álvarez-Errico D、Esteller M
单位
Cancer and Leukemia Epigenetics and Biology Program (PEBCL), Josep Carreras Leukaemia Research Institute (IJC), Badalona, Catalonia, Spain.Spain
文献类型
非美国政府资助研究
期刊
Journal of the National Cancer Institute2022 Jul 11
原文标识
PubMed 35438170 · DOI 10.1093/jnci/djac088