■嵌合抗原受体(CAR)T细胞和双特异性抗体(BsAb)是针对表达特异性抗原的细胞重定向免疫系统的主要平台。彻底改变血液恶性肿瘤的治疗方法,包括多发性骨髓瘤(MM)。在MM中,耐药复发是主要的治疗限制因素,也是导致该疾病仍被认为无法治愈的主要原因。T细胞参与疗法有望改善MM的治疗。然而,T细胞适应性可能会阻碍这些治疗的有效性。T细胞衰竭是效应子功能逐渐下降的条件,细胞因子分泌减少,和慢性抗原刺激引起的抑制性受体表达增加。
■这篇综述探讨了在T细胞重定向BsAb和CAR-T治疗的背景下,MM中T细胞耗竭的发现。
■T细胞的适应性已成为T细胞重定向疗法发展的重要因素。T细胞耗竭与这些疗法相关的方式可能会影响CAR和BsAbs技术的进一步发展。以及临床使用的策略。因此,这篇综述旨在探讨目前对MM中T细胞耗竭的认识及其与这些治疗的关系。
UNASSIGNED: Chimeric Antigen Receptor (CAR) T-cells and Bispecific Antibodies (BsAb) are the leading platforms for redirecting the immune system against cells expressing the specific antigen, revolutionizing the treatment of hematological malignancies, including multiple myeloma (MM). In MM, drug-resistant relapses are the main therapy-limiting factor and the leading cause of why the disease is still considered incurable. T-cell-engaging therapies hold promise in improving the treatment of MM. However, the effectiveness of these treatments may be hindered by T-cell fitness. T-cell exhaustion is a condition of a gradual decline in effector function, reduced cytokine secretion, and increased expression of inhibitory receptors due to chronic antigen stimulation.
UNASSIGNED: This review examines findings about T-cell exhaustion in MM in the context of T-cell redirecting BsAbs and CAR-T treatment.
UNASSIGNED: The fitness of T-cells has become an important factor in the development of T-cell redirecting therapies. The way T-cell exhaustion relates to these therapies could affect the further development of CAR and BsAbs technologies, as well as the strategies used for clinical use. Therefore, this review aims to explore the current understanding of T-cell exhaustion in MM and its relationship to these therapies.