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Impact of the immunomodulating peptide thymosin alpha 1 on multiple myeloma and immune recovery after hematopoietic stem cell transplantation

机译:免疫调节肽胸腺素α1对造血干细胞移植后多发性骨髓瘤和免疫恢复的影响

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摘要

Multiple myeloma (MM) is characterized by the accumulation of monoclonal plasma cells in the bone marrow and causes several immune alterations in patients. Thymosin alpha 1 (T alpha 1) is a thymic peptide that has been associated with immuno-stimulating properties. In addition, this peptide exerts anti-tumor effects in several cancer types. Beneficial effects of T alpha 1 administration have also been shown on immune reconstitution after hematopoietic stem cell transplantation (HSCT), a current treatment modality in hematological malignancies including MM. In this study, we observed a slight reduction in the proliferation of murine and human MM cell lines in the presence of T alpha 1 in vitro. However, using two immunocompetent murine MM models (5TGM1 and MOPC315.BM), we did not observe any impact of T alpha 1 administration on MM development in vivo. Furthermore, no beneficial effects of T alpha 1 treatment were observed on lymphocyte immune reconstitution after transfusion of human hematopoietic stem cells into immunodeficient mice. In conclusion, despite direct effects of T alpha 1 on human MM cell line proliferation in vitro, T alpha 1 did not exert anti-myeloma effects in vivo in the two murine models tested. Moreover, T alpha 1 failed to improve immune recovery in a xenogeneic HSCT model.
机译:多发性骨髓瘤(MM)的特征是骨髓中单克隆浆细胞的蓄积,并引起患者的几种免疫改变。胸腺素α1(T alpha 1)是一种胸腺肽,与免疫刺激特性有关。另外,该肽在几种癌症类型中发挥抗肿瘤作用。还显示了T alpha 1给药对造血干细胞移植(HSCT)后免疫重建的有益作用,造血干细胞移植是包括MM在内的血液系统恶性肿瘤的当前治疗方式。在这项研究中,我们观察到在体外存在T alpha 1时鼠和人MM细胞系的增殖略有减少。但是,使用两种具有免疫功能的小鼠MM模型(5TGM1和MOPC315.BM),我们没有观察到T alpha 1给药对体内MM发育的任何影响。此外,在将人造血干细胞输注到免疫缺陷小鼠后,未观察到T alpha 1处理对淋巴细胞免疫重建的有益作用。总之,尽管T alpha 1在体外对人MM细胞系增殖具有直接作用,但在所测试的两个鼠模型中,T alpha 1并未在体内发挥抗骨髓瘤作用。此外,T alpha 1无法提高异种HSCT模型中的免疫恢复。

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