Saitoh Anri, Narita Miwako, Watanabe Norihiro, Tochiki Nozomi, Satoh Noriyuki, Takizawa Jun, Furukawa Tatsuo, Toba Ken, Aizawa Yoshifusa, Shinada Shohji, Takahashi Masuhiro
Laboratory of Hematology and Oncology, Graduate School of Health Sciences, Niigata University, 2-746, Asahimachi-dori, 951-8518,Niigata, Japan.
Med Oncol. 2008;25(2):137-47. doi: 10.1007/s12032-007-9004-4. Epub 2007 Sep 11.
In order to establish an efficient gammadelta T cell-mediated immunotherapy for hematological malignancies, we attempted to evaluate cytotoxicity against tumor cells by gammadelta T cells, which were generated from blood cells of patients with myeloma and lymphoma by culturing with zoledronate and a low dose of IL-2. Although gammadelta T cells were expanded in patients with myeloma and lymphoma as well as normal persons, the amplification rates of gammadelta T cells before and after culturing varied from patient to patient in myeloma and lymphoma. gammadelta T cells generated in patients with myeloma and lymphoma showed a potent cytotoxic ability against myeloma/lymphoma cell lines as shown in gammadelta T cells generated in normal subjects. In addition, gammadelta T cells generated in a patient with myeloma showed a cytotoxic ability against self myeloma cells freshly prepared from bone marrow. However, the same gammadelta T cells were demonstrated to be non-cytotoxic to normal cells of the patient. These data demonstrated that gammadelta T cells, which could be expanded in vitro from blood cells of patients with myeloma and lymphoma by culturing with zoledronate and IL-2, possess a sufficient cytotoxic ability against tumor cells. These findings suggested that in vitro generated patients' gammadelta T cells could be applied to gammadelta T cell-mediated immunotherapy for hematological malignancies.
为了建立一种针对血液系统恶性肿瘤的高效γδT细胞介导的免疫疗法，我们试图评估由骨髓瘤和淋巴瘤患者血细胞经唑来膦酸和低剂量白细胞介素-2培养产生的γδT细胞对肿瘤细胞的细胞毒性。尽管骨髓瘤和淋巴瘤患者以及正常人的γδT细胞均有扩增，但骨髓瘤和淋巴瘤患者培养前后γδT细胞的扩增率因人而异。骨髓瘤和淋巴瘤患者产生的γδT细胞对骨髓瘤/淋巴瘤细胞系显示出强大的细胞毒性能力，与正常受试者产生的γδT细胞情况相同。此外，一名骨髓瘤患者产生的γδT细胞对从骨髓新鲜制备的自身骨髓瘤细胞显示出细胞毒性能力。然而，同样的γδT细胞对该患者的正常细胞无细胞毒性。这些数据表明，通过与唑来膦酸和白细胞介素-2培养可从骨髓瘤和淋巴瘤患者血细胞体外扩增的γδT细胞对肿瘤细胞具有足够的细胞毒性能力。这些发现提示，体外产生的患者γδT细胞可应用于血液系统恶性肿瘤的γδT细胞介导的免疫疗法。
