Department of Microbiology and Immunology and Pediatrics, Medical University of South Carolina, Charleston, SC, USA.
Expert Rev Proteomics. 2021 Sep;18(9):767-780. doi: 10.1080/14789450.2021.1992276. Epub 2021 Oct 17.
Cancer immunotherapy is a rapidly growing field with exponential advancement in engineered immune cell-based therapies. For instance, an engineered chimeric antigen receptor (CAR) can be introduced in T-cells or other immune cells and adoptively transferred to target and kill cancer cells in hematologic malignancies or solid tumors. The first CAR-T-cell (CAR-T) therapy has been developed against CD19, a B-cell marker expressed on lymphoma and lymphoblastic leukemia. To allow for personalized treatment, proteomics approaches could provide insights into biomarkers for CAR-T therapy efficacy and toxicity.
We researched the most recent technology methods of biomarker evaluation used in the laboratory and clinical setting. Publications of CAR-T biomarkers were then systematically reviewed to provide a narrative of the most validated biomarkers of CAR-T efficacy and toxicity. Examples of biomarkers include CAR-T functionality and phenotype as well as interleukin-6 and other cytokines.
Biomarkers of CAR-T efficacy and toxicity have been identified, but still need to be validated and standardized across institutions. Moreover, few are used in the clinical setting due to limitations in real-time technology. Expansion of biomarker research could provide better understanding of patient response and risk of life-threatening side effects with potential for improved precision medicine.
癌症免疫疗法是一个快速发展的领域,在工程化免疫细胞疗法方面取得了指数级的进展。例如,可以在 T 细胞或其他免疫细胞中引入工程化嵌合抗原受体(CAR),并将其过继转移以靶向和杀伤血液系统恶性肿瘤或实体瘤中的癌细胞。第一种嵌合抗原受体 T 细胞(CAR-T)疗法是针对 B 细胞标志物 CD19 开发的,该标志物在淋巴瘤和淋巴母细胞白血病上表达。为了实现个性化治疗,蛋白质组学方法可以深入了解 CAR-T 治疗疗效和毒性的生物标志物。
我们研究了实验室和临床环境中用于评估生物标志物的最新技术方法。然后系统地回顾了 CAR-T 生物标志物的出版物,以提供对 CAR-T 疗效和毒性最有效的生物标志物的叙述。生物标志物的例子包括 CAR-T 的功能和表型以及白细胞介素 6 和其他细胞因子。
已经确定了 CAR-T 疗效和毒性的生物标志物,但仍需要在各机构之间进行验证和标准化。此外,由于实时技术的限制,很少在临床环境中使用。扩大生物标志物研究可以更好地了解患者的反应和危及生命的副作用风险,并有潜力改善精准医学。