决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Cardiac Risk Without a Roadmap: Lack of Evidence-Based Guidance for Cardiovascular Toxicity of T-Cell Redirecting Therapies.
尽管 CAR-T 和双特异性 T 细胞衔接器的心血管毒性已有描述,但由于各研究间不良事件定义和监测不一致,报告的发病率差异很大。
综述目的:T细胞重定向疗法已革新多种血液系统恶性肿瘤的治疗。这类疗法包括CAR-T细胞疗法(过继免疫治疗,通过工程化改造患者T细胞,使其表达针对肿瘤表面抗原的合成受体)以及双特异性T细胞衔接器(可同时靶向CD3和肿瘤特异性抗原的抗体)。两种方法均可将T细胞重新引导至肿瘤细胞,增强抗肿瘤免疫,且不受主要组织相容性复合体类别限制。随着适应证扩大,接受治疗的人群正扩展至年龄更大、体能状况更差、未被关键注册试验充分代表的患者,因此合并症负担较重患者的毒性谱值得关注。 近期发现:CAR-T和双特异性T细胞衔接器相关心血管毒性已有报道,但由于不同研究对不良事件定义和监测不一致,报告发生率差异很大。此外,多数研究排除了既往有心力衰竭或心肌病的患者。因此,对于这一日益扩大的亚组,目前缺乏基于证据的风险分层、围治疗期管理或监测指南。本文简要回顾T细胞重定向疗法相关心血管毒性,并指出临床试验入选标准的局限。我们进一步强调,亟需统一心血管毒性的定义,并针对既往心力衰竭或心肌病患者这一独立高危人群开展专门研究。
PURPOSE OF REVIEW: T-cell redirecting therapies have revolutionized the treatment of several hematologic malignancies. These include CAR T-cell therapy, an adoptive immunotherapy in which a patient's T-cells are engineered to express synthetic receptors against tumor surface antigens, and bispecific T-cell engagers, antibodies simultaneously targeting CD3 and a tumor-specific antigen. Both approaches redirect T-cells toward tumor cells, thereby enhancing anti-tumor immunity independent of major histocompatibility complex class restriction. With expanding indications, their use is extending into older and less fit populations than those represented in pivotal trials, raising important questions regarding toxicity profiles in patients with greater comorbidity burden. RECENT FINDINGS: Although cardiovascular toxicities of CAR T and bispecific T-cell engagers have been described, reported incidences are highly variable due to inconsistencies in adverse event definitions and surveillance across studies. Further, most studies have excluded patients with pre-existing heart failure or cardiomyopathy. Consequently, there is a lack of evidence-based guidance for risk stratification, peri-treatment management, or monitoring in this growing subgroup. Here, we briefly review the cardiovascular toxicities associated with T-cell redirecting therapies and highlight limitations in clinical trial inclusion criteria. We then emphasize the urgent need for uniformity in defining cardiovascular toxicities, as well as for dedicated studies in patients with pre-existing heart failure or cardiomyopathy as a distinct high-risk population.
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