Mukherji B, Arnbjarnarson O, Spitznagle L A, Kalish R I, Hoffman J, Ergin M T, Spencer R P
Department of Medicine (Oncology), University of Connecticut Health Center, Farmington 06032.
Int J Rad Appl Instrum B. 1988;15(4):419-27. doi: 10.1016/0883-2897(88)90012-8.
In vivo patterns of lymphocytes sensitized against autologous tumor (in vitro) were studied in seven patients with metastatic cancer as a potential candidate for an alternative method of radioimmunodetection and adoptive immunocytotherapy. Peripheral blood lymphocytes (PBL) were either activated in Interleukin-2 (IL-2) [lymphokine activated killer (LAK) cells] or sensitized against autologous tumor cells by in vitro co-culture (IVC) and expanded in IL-2 (educated cells); both were then labelled with 111In. Labelled autologous cells (1 x 10(7)-5 x 10(8)) were administered to patients and biodistribution studied by imaging under a gamma camera at various time intervals. In 4/7 cases, imaging with the educated cells showed concentrations of radioactivity at sites that correlated positively with clinically detectable metastatic tumor. By contrast, only one instance of positive uptake was seen with the LAK cells. Other than slight fever in three cases, infusions of labelled PBL were well tolerated. Educated lymphocytes were cytotoxic against autologous tumor cells and the cytotoxic reactivities of the educated cells were maintained in continuous culture in IL-2 for 4-6 weeks. Evidence of accumulation of radiolabelled educated autologous cells at a significantly higher frequency than that of the LAK cells suggests that in vitro expanded educated PBL might be better candidates for radioimmunodetection of human cancer, and continuous cultures of such educated autologous PBL might be sources for repeated administration of these effector cells.
作为放射免疫检测和过继免疫细胞治疗替代方法的潜在候选者，我们研究了7例转移性癌症患者体内对自体肿瘤（体外）致敏的淋巴细胞模式。外周血淋巴细胞（PBL）要么在白细胞介素-2（IL-2）中激活（淋巴因子激活的杀伤细胞[LAK细胞]），要么通过体外共培养（IVC）对自体肿瘤细胞致敏并在IL-2中扩增（培养细胞）；然后两者都用铟-111标记。将标记的自体细胞（1×10⁷-5×10⁸）注入患者体内，并在不同时间间隔通过γ相机成像研究其生物分布。在7例中的4例中，用培养细胞成像显示放射性浓度在与临床可检测到的转移性肿瘤呈正相关的部位。相比之下，LAK细胞仅出现1例阳性摄取。除3例出现低热外，标记的PBL输注耐受性良好。培养的淋巴细胞对自体肿瘤细胞具有细胞毒性，并且培养细胞的细胞毒性反应性在IL-2中连续培养4至6周仍得以维持。放射性标记的培养自体细胞积累的证据表明其频率明显高于LAK细胞，这表明体外扩增的培养PBL可能是人类癌症放射免疫检测的更好候选者，并且这种培养的自体PBL的连续培养可能是这些效应细胞重复给药的来源。
