Dessureault S, Graham F L, Gallinger S
Department of Surgery, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Ontario, Canada.
Cancer Gene Ther. 1999 May-Jun;6(3):195-208. doi: 10.1038/sj.cgt.7700018.
Transfection of the costimulatory molecule B7-1 (CD80) into murine tumors can increase antitumor immunity and eradicate tumor growth. The purpose of this study was to test autologous lymphocyte responses against freshly resected human cancers infected in vitro with an adenovirus vector expressing the B7-1 molecule (AdB7). Resected tumors (sarcomas, adenocarcinomas, melanomas, and multiple myelomas) were disaggregated into single-cell suspensions and divided into three groups: (a) native, noninfected tumor cells (TM); (b) AdB7-infected, B7-1(+) tumor cells (TMB7); and (c) control Addl70.3-infected, B7-1(-) tumor cells (TMAd). B7-1 expression was verified by flow cytometry. Autologous peripheral blood lymphocytes from these patients were tested for proliferative and cytotoxic activity against the three tumor groups. There was an increased lymphocyte-proliferative response against B7-1(+) tumor cells, particularly in the presence of interleukin-12 (IL-12) or low-dose IL-2. B7-1(+) tumor cells were also killed more efficiently than B7-1(-) tumor cells in natural killer cell-mediated cytotoxicity assays, and this was most significant when lymphocytes had been pretreated with IL-12. Human natural killer cells were found to express CD28, a receptor for B7-1. The high efficiency of AdB7-mediated gene transfer and the augmented B7-1-mediated lymphocyte responses suggest that AdB7 vectors may be effective in human cancer immunotherapy.
将共刺激分子B7-1（CD80）转染到鼠肿瘤中可增强抗肿瘤免疫力并消除肿瘤生长。本研究的目的是检测针对体外被表达B7-1分子的腺病毒载体（AdB7）感染的新鲜切除的人类癌症的自体淋巴细胞反应。将切除的肿瘤（肉瘤、腺癌、黑色素瘤和多发性骨髓瘤）解离成单细胞悬液，并分为三组：（a）天然未感染的肿瘤细胞（TM）；（b）AdB7感染的、B7-1（+）肿瘤细胞（TMB7）；以及（c）对照Addl70.3感染的、B7-1（-）肿瘤细胞（TMAd）。通过流式细胞术验证B7-1的表达。检测这些患者的自体外周血淋巴细胞对这三组肿瘤的增殖和细胞毒性活性。对B7-1（+）肿瘤细胞的淋巴细胞增殖反应增强，特别是在存在白细胞介素-12（IL-12）或低剂量IL-2的情况下。在自然杀伤细胞介导的细胞毒性试验中，B7-1（+）肿瘤细胞也比B7-1（-）肿瘤细胞更有效地被杀死，当淋巴细胞用IL-12预处理时，这种情况最为显著。发现人类自然杀伤细胞表达B7-1的受体CD28。AdB7介导的基因转移的高效率和增强的B7-1介导的淋巴细胞反应表明AdB7载体可能在人类癌症免疫治疗中有效。
