A new strategy for treatment of malignant tumor:: Intra-bone marrow-bone marrow transplantation plus CD4- donor lymphocyte infusion
A new strategy for treatment of malignant tumor:: Intra-bone marrow-bone marrow transplantation plus CD4- donor lymphocyte infusion
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DOI：
10.1634/stemcells.2004-0258
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发表时间：
2005-03-01
期刊：
影响因子：
5.2
通讯作者：
Ikehara, S
中科院分区：
文献类型：
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作者：
Suzuki, Y;Adachi, Y;Ikehara, S
供体淋巴细胞输注（DLI）临床上用于治疗恶性肿瘤。我们最近发现，即使在减少辐射剂量的情况下，骨髓内骨髓移植（IBM-BMT）也可以用于治疗各种自身免疫性疾病。此外，最近我们发现IBM-BMT不仅可以预防移植失败，还可以预防移植物抗宿主病（GvHD）。基于这些发现，我们尝试通过 DLI 联合 IBM-BMT 来预防和治疗肿瘤（Meth-A 细胞系：BALB/c 来源的纤维肉瘤）的进展。当肿瘤生长到约10 x 10 mm时，对荷瘤BALB/c (H-2(d))小鼠进行5 Gy照射，然后将来自C57BL/6J (B6) (H-2(b))小鼠的全脾细胞（作为DLI）静脉注射到BALB/c小鼠中。同时，将来自 B6 小鼠的骨髓细胞 (BMC) 直接注射到 BALB/c 小鼠 (IBM-BMT) 的骨髓腔中。肿瘤尺寸减小，但小鼠死于 GvHD。然而，当将去除 CD4(+) T 细胞的脾细胞用于 DLI 时，由于肿瘤生长缓慢，受者仅表现出轻微的 GvHD，并且存活时间更长。相比之下，当使用去除CD8(+) T细胞的脾细胞进行DLI时，受者表现出比注射完整脾细胞的受者更严重的GvHD。这些结果表明 IBM-BMT 联合 DLI（特定细胞群（如 CD4+T 细胞）的消耗或减少）可能有助于抑制 GvHD 和肿瘤生长。
Donor lymphocyte infusion (DLI) is clinically used for the treatment of malignant tumors. We have found recently that intra-bone marrow-bone marrow transplantation (IBM-BMT) can be used to treat various autoimmune diseases, even when radiation doses are reduced. In addition, recently we have found that IBM-BMT can prevent not only graft failure but also graft-versus-host disease (GvHD). Based on these findings, we attempted to prevent and treat the progression of a tumor (Meth-A cell line: BALB/c-derived fibrosarcoma) by DLI plus IBM-BMT. When the tumors had grown to approximately 10 x 10 mm, the tumor-bearing BALB/c (H-2(d)) mice were irradiated with 5 Gy, and whole spleen cells from C57BL/6J (B6) (H-2(b)) Mice (as DLI) were then intravenously injected into the BALB/c mice. Simultaneously, bone marrow cells (BMCs) from B6 mice were injected directly into the bone marrow cavity of the BALB/c mice (IBM-BMT). The tumors decreased in size, but the mice died of GvHD. However, when CD4(+) T-cell-depleted spleen cells were used for DLI, the recipients showed only mild GvHD and survived longer, due to the slow growth of the tumor. In contrast, when CD8(+) T-cell-depleted spleen cells were used for DLI, the recipients showed more severe GvHD than those injected with whole spleen cells. These results suggest that IBM-BMT plus DLI (the depletion or reduction of a certain cell population like CD4(+) T cells) could be helpful to suppress both GvHD and tumor growth.