X-box binding protein 1 (XBP1), CD138 (Syndecan-1) and CS1 (SLAMF7) are highly expressed antigens in cancers including multiple myeloma (MM). Here, we identify and characterize immunogenic HLA-A24 peptides derived from these antigens for potential vaccination therapy of HLA-A24+ patients with MM. The identified immunogenic HLA-A24-specific XBP1 unspliced (UN)_185-193 (I S P W I L A V L), XBP1 spliced (SP)_223-231 (V Y P E G P S S L), CD138_265-273 (I F A V C L V G F) and CS1_240-248 (L F V L G L F L W) peptides induced antigen-specific CTL with anti-MM activity in an HLA-A24 restricted manner. Furthermore, a cocktail containing the four HLA-A24 peptides evoked MM-specific CTL with distinct phenotypic profiles (CD28, CD40L, 41BB, CD38, CD69) and anti-tumor activities, evidenced by perforin upregulation, CD107a degranulation (cytotoxicity) and Th1-type cytokines (IFN-γ/IL-2/TNF-α) production in response to HLA-A24⁺ MM cells. The multipeptide-specific CTL included antigen-specific memory CD8⁺ T cells expressing both T-cell activation (CD38, CD69) and immune checkpoints antigens (CTLA, PD-1, LAG-3, TIM-3). These results provide the framework for a multipeptide vaccination therapy to induce tumor-specific CTL in HLA-A24-positive patients with myeloma and other cancers expressing these antigens.

中文翻译：

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HLA-A24 特异性 XBP1、CD138 (Syndecan-1) 和 CS1 (SLAMF7) 肽的鉴定和表征，诱导针对多发性骨髓瘤的抗原特异性记忆细胞毒性 T 淋巴细胞。


X-box 结合蛋白 1 (XBP1)、CD138 (Syndecan-1) 和 CS1 (SLAMF7) 是包括多发性骨髓瘤 (MM) 在内的癌症中高表达的抗原。在这里，我们鉴定并表征了源自这些抗原的免疫原性 HLA-A24 肽，用于 HLA-A24+ 多发性骨髓瘤患者的潜在疫苗接种治疗。鉴定出免疫原性 HLA-A24 特异性 XBP1 未剪接 (UN) _185-193 (ISPWILAVL)、XBP1 剪接 (SP) _223-231 (VYPEGPSSL)、CD138 _265-273 (IFAVCLVGF) 和 CS1 _240-248 (LFVLGLFLW) 肽诱导抗原-以HLA-A24限制方式具有抗MM活性的特异性CTL。此外，含有四种 HLA-A24 肽的混合物可诱发具有不同表型特征（CD28、CD40L、41BB、CD38、CD69）和抗肿瘤活性的 MM 特异性 CTL，穿孔素上调、CD107a 脱颗粒（细胞毒性）和 Th1- 证明了这一点。 HLA-A24 ⁺ MM 细胞响应型细胞因子（IFN-γ/IL-2/TNF-α）的产生。多肽特异性 CTL 包括表达 T 细胞激活（CD38、CD69）和免疫检查点抗原（CTLA、PD-1、LAG-3、TIM-3）的抗原特异性记忆 CD8 ⁺ T 细胞。这些结果为多肽疫苗接种疗法提供了框架，以在患有骨髓瘤和表达这些抗原的其他癌症的 HLA-A24 阳性患者中诱导肿瘤特异性 CTL。