CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Immune status and selection of patients for immunotherapy in myeloma: a proposal.
Immune status and selection of patients for immunotherapy in myeloma: a proposal.
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基于招募和重定向内源性和/或合成免疫(如CAR-T 细胞或双特异性抗体)的新型免疫治疗方法正在改变多发性骨髓瘤(MM)的临床管理。免疫系统对骨髓瘤治疗抗肿瘤效应的贡献也日益受到重视。MM 的临床恶性起源于骨髓瘤发生早期开始的全身免疫改变以及受空间结构影响的区域免疫变化。免疫细胞的预先存在和治疗诱导的变化与 MM 患者的结局相关,包括免疫治疗后的结局。
在此,我们讨论关于 MM 患者免疫状态和免疫治疗后结局的现有数据的见解和局限性。全身和/或区域免疫的预先存在变异正在成为当前免疫治疗以及疫苗疗效的主要决定因素。
然而,MM 是一种多灶性恶性肿瘤。与实体瘤一样,整合肿瘤的空间方面以及考虑免疫靶点与免疫细胞生物学可能对于优化免疫治疗(包括 T 细胞重定向)在 MM 中的应用至关重要。
我们提出 5 种不同的 MM 空间免疫类型,可能为 MM 中特定免疫治疗的最佳应用提供初步框架:免疫耗竭型、免疫允许型、免疫排斥型、免疫抑制型和免疫抵抗型。这些考虑也可能有助于优化新兴免疫治疗的合理患者选择以改善结局。
Newer immune-based approaches based on recruitment and redirection of endogenous and/or synthetic immunity such as chimeric antigen receptor T cells or bispecific antibodies are transforming the clinical management of multiple myeloma (MM). Contributions of the immune system to the antitumor effects of myeloma therapies are also increasingly appreciated.
Clinical malignancy in MM originates in the setting of systemic immune alterations that begin early in myelomagenesis and regional changes in immunity affected by spatial contexture. Preexisting and therapy-induced changes in immune cells correlate with outcomes in patients with MM including after immune therapies.
Here, we discuss insights from and limitations of available data about immune status and outcomes after immune therapies in patients with MM. Preexisting variation in systemic and/or regional immunity is emerging as a major determinant of the efficacy of current immune therapies as well as vaccines.
However, MM is a multifocal malignancy. As with solid tumors, integrating spatial aspects of the tumor and consideration of immune targets with the biology of immune cells may be critical to optimizing the application of immune therapy, including T-cell redirection, in MM.
We propose 5 distinct spatial immune types of MM that may provide an initial framework for the optimal application of specific immune therapies in MM: immune depleted, immune permissive, immune excluded, immune suppressed, and immune resistant. Such considerations may also help optimize rational patient selection for emerging immune therapies to improve outcomes.
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