Sporn J R, Ergin M T, Robbins G R, Cable R G, Silver H, Mukherji B
Department of Medicine, University of Connecticut Health Center, Farmington 06030.
Cancer Immunol Immunother. 1993 Aug;37(3):175-80. doi: 10.1007/BF01525432.
A clinical trial of adoptive immunotherapy was carried out with peripheral blood lymphocytes (PBL), cocultured in vitro with autologous tumor cells and interleukin-2 (IL-2), in 14 patients with advanced melanoma. PBL from these patients were cocultured with irradiated autologous tumor cells for 7 days, which was followed by expansion in IL-2-containing medium. These lymphocytes were returned to the patient along with intravenous IL-2 at doses up to 2 x 10(6) IU m-2 day-1. A dose of 300 mg/m2 cyclophosphamide was administered to each patient intravenously 4 days prior to each treatment. Following coculture, the lymphocytes were primarily CD3+ T cells and they expressed varied degrees of cytotoxicity against autologous melanoma cells. In 9 patients the activated cells were at least 80% CD4+ and in 2 cases they were mostly CD8+. Some of the activated cells exhibited suppressor or helper activity in a functional regulatory coculture assay. No major therapeutic response was observed in this study. Minor responses were observed in 2 patients. Toxicities were those expected from the IL-2 dose administered.
对14例晚期黑色素瘤患者进行了过继性免疫治疗的临床试验,采用外周血淋巴细胞(PBL),将其与自体肿瘤细胞和白细胞介素-2(IL-2)在体外共培养。这些患者的PBL与经照射的自体肿瘤细胞共培养7天,随后在含IL-2的培养基中扩增。这些淋巴细胞与静脉注射剂量高达2×10⁶IU m⁻²天⁻¹的IL-2一起回输到患者体内。在每次治疗前4天,给每位患者静脉注射300mg/m²的环磷酰胺。共培养后,淋巴细胞主要为CD3⁺ T细胞,它们对自体黑色素瘤细胞表现出不同程度的细胞毒性。9例患者中活化细胞至少80%为CD4⁺,2例患者中活化细胞主要为CD8⁺。在功能调节共培养试验中,一些活化细胞表现出抑制或辅助活性。本研究未观察到主要治疗反应。2例患者观察到轻微反应。毒性反应为所给予IL-2剂量预期出现的反应。