A novel dual-cytokine-antibody fusion protein, consisting of an antibody directed against CD38 [a tumor-associated antigen mainly expressed on the surface of multiple myeloma (MM) cells], simultaneously fused to both tumor necrosis factor ligand superfamily member 10 (TRAIL) and interleukin-2 (IL2), was designed, expressed and purified to homogeneity. The novel fusion protein, termed IL2-αCD38-αCD38-scTRAIL, was able to selectively recognize its cognate antigen expressed on the surface of MM and lymphoma cell lines, as evidenced by flow cytometry analysis. Moreover, the targeted version of TRAIL was able to induce cancer cell death in vitro, both with MM cell lines and with fresh isolates from the bone marrow of MM patients. The experiments provide a rationale for possible future applications of IL2-αCD38-αCD38-scTRAIL for the treatment of patients with MM or other CD38-positive malignancies.

中文翻译：

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一种用于治疗 CD38 阳性恶性肿瘤的新型双细胞因子抗体融合蛋白。

一种新型双细胞因子抗体融合蛋白，由一种针对 CD38 的抗体（一种主要在多发性骨髓瘤 (MM) 细胞表面表达的肿瘤相关抗原）组成，同时与肿瘤坏死因子配体超家族成员 10 (TRAIL) 融合) 和白细胞介素 2 (IL2) 被设计、表达和纯化至同质。流式细胞术分析证明，这种称为 IL2-αCD38-αCD38-scTRAIL 的新型融合蛋白能够选择性地识别其在 MM 和淋巴瘤细胞系表面上表达的同源抗原。此外，TRAIL 的靶向版本能够在体外诱导癌细胞死亡，包括 MM 细胞系和来自 MM 患者骨髓的新鲜分离物。