Mukaide Hiromi, Adachi Yasushi, Koike-Kiriyama Naoko, Suzuki Yasuhiro, Minamino Keizo, Iwasaki Masayoshi, Tsuda Masanobu, Nakano Keiji, Koike Yasushi, Shigematsu Akio, Kamiyama Yasuo, Ikehara Susumu
First Department of Pathology, Kansai Medical University, Moriguchi City, Osaka, Japan.
Int J Oncol. 2007 Jun;30(6):1309-15.
We have previously shown that the combination of allogeneic intra-bone marrow-bone marrow transplantation (IBM-BMT) and donor lymphocyte infusion (DLI) using CD4+ cell-depleted spleen cells is effective in suppressing tumor growth, but that this does not induce graft-versus-host disease (GVHD) in mice. In this report, we show that formalin-fixed tumor cell-pulsed dendritic cells (FFTCP DCs) have an additive effect with IBM-BMT plus DLI on the suppression of tumor growth, but that the DCs do not augment GVHD. BALB/c mice, which had been subcutaneously inoculated with Meth A (BALB/c-derived fibrosarcoma), were irradiated at a low dose (5 Gy) and were transplanted with bone marrow cells (BMCs) from C57BL/6 (B6) mice into the bone marrow cavity (IBM-BMT). Simultaneously, the mice were intravenously injected with spleen cells from B6 mice, and subcutaneously injected with FFTCP DCs derived from the bone marrow (BM) of B6 mice. At the point of the induction of DCs from BMCs, formalin-fixed Meth A cells were added into the culture. The mice treated with the combination of FFTCP DCs, IBM-BMT and DLI using CD4+ cell-depleted spleen cells showed smaller tumor sizes and longer survival than the mice treated with IBM-BMT plus FFTCP DCs or IBM-BMT plus DLI using CD4+ cell-depleted spleen cells. These results suggest that the combination of FFTCP DCs, IBM-BMT plus DLI using CD4+ cell-depleted spleen cells has potent anti-tumor effects without showing GVHD.
我们之前已经表明，使用去除CD4+细胞的脾细胞进行同种异体骨髓内骨髓移植（IBM-BMT）和供体淋巴细胞输注（DLI）的联合治疗可有效抑制肿瘤生长，且不会在小鼠中诱发移植物抗宿主病（GVHD）。在本报告中，我们表明福尔马林固定的肿瘤细胞脉冲树突状细胞（FFTCP DCs）与IBM-BMT加DLI联合使用时，对肿瘤生长的抑制具有相加作用，但这些DCs不会增强GVHD。将皮下接种了Meth A（源自BALB/c的纤维肉瘤）的BALB/c小鼠以低剂量（5 Gy）进行照射，并将来自C57BL/6（B6）小鼠的骨髓细胞（BMCs）移植到骨髓腔中（IBM-BMT）。同时，给小鼠静脉注射来自B6小鼠的脾细胞，并皮下注射源自B6小鼠骨髓（BM）的FFTCP DCs。在从BMCs诱导DCs时，将福尔马林固定的Meth A细胞添加到培养物中。与使用IBM-BMT加FFTCP DCs或使用去除CD4+细胞的脾细胞进行IBM-BMT加DLI治疗的小鼠相比，使用FFTCP DCs、IBM-BMT和去除CD4+细胞的脾细胞进行DLI联合治疗的小鼠肿瘤体积更小，生存期更长。这些结果表明，FFTCP DCs、IBM-BMT加使用去除CD4+细胞的脾细胞进行DLI的联合治疗具有强大的抗肿瘤作用，且不会表现出GVHD。
