Immunoenhancing properties of the anti-tumor effects of adoptively transferred T cells with chemotherapeutic cyclophosphamide by co-administration of bone marrow cells

Mohamed L. Salem , Soha G.R. Abdel Salam , Mohamed Nassef , Said Hammad , Rania El Adl
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引用次数: 4

Abstract

In this study we aimed to determine the anti-tumor efficacy of co-treatment of adoptively transferred T cells with bone marrow either harvested from naïve mice or G-CSF activated after treatment with the anti-cancer drug cyclophosphamide (CTX) as a source enriched in stem cells. CTX-treated Swiss Albino (CD-1) mice were injected with 2 × 105 Ehrlich ascetic carcinoma (EAC) cell line and then adoptively transferred with in vitro co-activated T cells with or without bone marrow one day post CTX treatment. All mice were vaccinated with tumor lysate and Hiltonol®. The results showed that co-transfer of activated T cells with bone marrow provided the highest antitumor effect and induced marked increase in numbers of splenocytes, leucocytes and bone marrow cells. Interestingly, T cells derived from EAC tumor-bearing host induced higher effects than those from normal mice. In sum, our data suggest that combination of CTX and activated transferred T cells with bone marrow induces proliferation and expansion of immune cells, which are functional and can be exploited in vivo to foster more effective antitumor adoptive immunotherapy strategies.

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骨髓细胞与化疗环磷酰胺过继转移T细胞抗肿瘤作用的免疫增强特性
在这项研究中,我们旨在确定过继转移T细胞与naïve小鼠骨髓或抗癌药物环磷酰胺(CTX)作为干细胞富集源后活化的G-CSF共同治疗的抗肿瘤效果。CTX处理的瑞士白化病(CD-1)小鼠注射2 × 105埃利希行囊性癌(EAC)细胞系,然后在CTX处理后1天与体外共活化T细胞(含或不含骨髓)过继转移。所有小鼠均接种肿瘤裂解液和Hiltonol®。结果表明,活化T细胞与骨髓共转移抗肿瘤效果最好,可诱导脾细胞、白细胞和骨髓细胞数量显著增加。有趣的是,来自EAC荷瘤宿主的T细胞诱导的效应高于来自正常小鼠的T细胞。综上所述,我们的数据表明CTX和活化的转移T细胞与骨髓结合可诱导免疫细胞的增殖和扩增,这是功能性的,可以在体内开发更有效的抗肿瘤过继免疫治疗策略。
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47 weeks
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