Allogeneic cell therapy from immuniz ed donors with tumor antigen peptide enhances the antitumor effect after cyclophosphamide-using non-myeloabl ative allogeneic hematopoietic cell transplantation
Allogeneic cell therapy from immuniz ed donors with tumor antigen peptide enhances the antitumor effect after cyclophosphamide-using non-myeloabl ative allogeneic hematopoietic cell transplantation
复制标题
免疫供体的肿瘤抗原肽同种异体细胞治疗增强环磷酰胺非清髓性同种异体造血细胞移植后的抗肿瘤效果
DOI：
10.1111/j.1349-7006.2008.01014.x
复制
发表时间：
2009
期刊：
影响因子：
5.7
通讯作者：
Eto M 他8名
中科院分区：
文献类型：
--
作者：
Hamaguchi M;Eto M 他8名
非清髓性异基因干细胞移植是治疗恶性血液病和实体瘤的一种选择。我们最近提出了一种使用环磷酰胺的非清髓性细胞疗法，其中在对供体细胞诱导耐受后进行供体淋巴细胞输注（DLI）。在这项研究中，我们测试了在DLI之前通过供体的预免疫来增强使用环磷酰胺的细胞疗法的可能性。我们最初评估了使用环磷酰胺的细胞疗法是否也可以对皮下建立的结肠26癌显示出抗肿瘤作用。作为结肠26的肿瘤抗原衍生肽，我们使用AH 1，一种源自内源性鼠白血病病毒包膜蛋白（gp 70）的免疫显性H-2Ld结合肽。将来自用AH 1肽预免疫的供体的DLI的使用环磷酰胺的细胞疗法与来自未免疫小鼠的DLI进行比较。使用环磷酰胺的细胞疗法显著抑制皮下建立的结肠26癌，并且肿瘤排斥小鼠获得了肿瘤特异性保护性免疫。当与来自用AH 1免疫的供体的DLI组合时，使用细胞疗法的环磷酰胺的抗肿瘤作用显著增强。来自肿瘤肽免疫供体的DLI显示对供体嵌合体和处理小鼠的体重没有影响，表明移植物抗宿主病的风险没有增加。肿瘤特异性细胞毒性T淋巴细胞可以从肿瘤排斥小鼠中产生。我们的研究结果表明，使用环磷酰胺的非清髓性细胞治疗与来自肿瘤肽免疫供体的DLI是一种有用的方案，可增强移植物抗肿瘤效应，而不会加重移植物抗宿主病。（Cancer Sci2009; 100：138-143）
Non‐myeloablative allogeneic stem cell transplantation is an option for the treatment of hematological malignancies as well as solid tumors. We recently proposed a cyclophosphamide‐using non‐myeloablative cell therapy in which donor lymphocytes infusion (DLI) was carried out after tolerance induction to donor cells. In this study, we tested the possibility that the cyclophosphamide‐using cell therapy could be augmented by pre‐immunization of donors before DLI. We initially assessed whether or not the cyclophosphamide‐using cell therapy could also show antitumor effect against subcutaneously established colon 26 carcinoma. As a tumor antigen‐derived peptide for colon 26, we used AH1, an immunodominant H‐2Ld‐binding peptide derived from the envelope protein (gp70) of an endogenous murine leukemia virus. The cyclophosphamide‐using cell therapy with the DLI from donors which were pre‐immunized with the AH1 peptide was compared with that from non‐immunized mice. The cyclophosphamide‐using cell therapy significantly suppressed subcutaneously established colon 26 carcinoma, and the tumor‐rejected mice acquired the tumor‐specific protective immunity. When combined with the DLI from donors that were immunized with AH1, antitumor effect of the cyclophosphamide‐using cell therapy was significantly augmented. The DLI from tumor peptide‐immunized donors showed no influence on donor chimerism and bodyweight of the treated mice, indicating no increased risk of graft‐versus‐host disease. Tumor‐specific cytotoxic T lymphocytes could be generated from tumor‐rejected mice. Our results indicate that the cyclophosphamide‐using non‐myeloablative cell therapy with the DLI from tumor peptide‐immunized donors is a useful protocol to augment graft‐versus‐tumor effect without exacerbation of graft‐versus‐host disease. (Cancer Sci2009; 100: 138–143)