Dual-antigen-targeting T-cell immunotherapies in MM: circumventing tumor heterogeneity and preventing antigen escape.

Despite these advances, a subset of patients does not respond, and most patients will eventually relapse.

尽管取得了这些进展，但仍有一部分患者没有反应，而且大多数患者最终会复发。

Tumor heterogeneity, resulting in rapid selection of both antigen-negative and antigen-low cells, is a critical issue affecting response to T-cell immunotherapies targeting single tumor-associated antigens.

肿瘤异质性，导致抗原阴性和抗原低表达细胞的快速选择，是影响针对单一肿瘤相关抗原的T细胞免疫治疗反应的一个关键问题。

In addition, antigen escape (due to deletions, mutations, or epigenetic alterations) is frequently observed in patients who experience disease progression after chimeric antigen receptor (CAR) T-cell infusion or during bispecific antibody (BsAb) treatment.

此外，在接受嵌合抗原受体（CAR）T细胞输注后或双特异性抗体（BsAb）治疗期间疾病进展的患者中，经常观察到由于缺失、突变或表观遗传改变导致的抗原逃逸。

Simultaneous targeting of 2 tumor-associated antigens may improve efficacy by addressing heterogeneous target expression and preventing antigen escape.

同时针对2个肿瘤相关抗原可能会通过解决异质性靶点表达和防止抗原逃逸来提高疗效。

Various dual-targeting strategies are currently evaluated in MM, including the combination of 2 single-antigen-targeting BsAbs.

目前在多发性骨髓瘤中评估了多种双靶向策略，包括2个单抗原靶向双特异性抗体的组合。

Of note, the efficacy of the combination of teclistamab and talquetamab appears to have enhanced anti-MM activity, compared with the corresponding conventional BsAbs alone in similar patient populations.

值得注意的是，teclistamab和talquetamab的联合使用似乎比单独使用相应的传统双特异性抗体在类似患者群体中具有更强的抗多发性骨髓瘤活性。

Furthermore, dual-antigen targeting with T-cell-redirecting trispecific antibodies (eg, ramantamig [BCMA×GPRC5D] and ISB 2001 [BCMA×CD38]) has already demonstrated promising results in heavily pretreated MM.

此外，使用T细胞重定向的三特异性抗体（例如ramantamig [BCMA×GPRC5D]和ISB 2001 [BCMA×CD38]）进行双重抗原靶向已经在经过重度预处理的多发性骨髓瘤患者中显示出有希望的结果。

Studies with limited numbers of patients have demonstrated that CAR T-cell products with specificity for >1 antigen are also effective in advanced MM; however, at this time, none of the dual-targeting CAR T-cell products has been shown to be clearly superior to targeting BCMA alone with ciltacabtagene autoleucel.

针对超过一个抗原特异性的CAR T细胞产品在晚期多发性骨髓瘤中的有效性已在患者数量有限的研究中得到证实；然而，目前尚无任何双靶向CAR T细胞产品被证明明显优于单独靶向BCMA的ciltacabtagene autoleucel。

Dual targeting should eventually be compared in large phase 3 trials with the classical approach of serial treatment with monotargeting agents with target switch.

最终应在大型III期试验中比较双靶向与经典方法，即使用单靶向药物进行序贯治疗并切换靶点。