ADOPTIVE IMMUNOTHERAPY UTILIZING LAK CELLS & IL-2 ADMINISTERED INTRAPERITONEALLY

我们试图提高LAK + IL-2治疗的疗效， 将其腹膜内给予癌症患者， 这个解剖空间。 患者接受预充， 白细胞介素-2和收获LAK前体细胞，如 系统性LAK和IL-2试验。 这些细胞被注射到 腹膜内注射，每天一次，共沿着5天， 每八小时注射一次每公斤25,000单位 十 可评估的结肠癌患者中，5例有部分缓解， 在9名卵巢癌患者中，2名患者部分缓解。 所有反应均通过腹腔镜检查或剖腹手术进行判断 并且往往持续时间较短（四个月）。 毒性作用 这种治疗的效果与在患者中观察到的相似。 全身接受LAK和IL-2治疗， 我们的病人通常会出现弥漫性腹部肿胀， 腹部反跳痛。 LAK细胞活性未维持在 除非给予白细胞介素-2， 同时。 腹腔内有LAK活性 至少连续5天，同时IL-2被 管理。 活动回落到基线约48 IL-2的腹膜内输注停止后24小时。 腹腔液中γ干扰素水平明显升高 并且有来自体内单核细胞活化的证据。 腹膜内纤维化限制了治疗， 大约三个周期。 我们得出结论，这种疗法是 有效地引起肿瘤反应， 容忍。 然而，腹膜腔中的纤维化将 最终阻止了这种治疗的有效实施。

We sought to improve the efficacy of LAK + IL-2 therapy by administering it intraperitoneally to patients with cancer limited to this anatomic space. Patients underwent priming with interleukin-2 and harvesting of LAK precursor cells as is done on the systemic LAK and IL-2 trials. The cells were administered intraperitoneally daily for five days along with interleukin-2 at a dose of 25,000 units per kilograms every eight hours. Of ten evaluable colon carcinoma patients, five had partial responses, and of nine patients with ovarian carcinoma, two had partial responses. All responses were judged either by peritoneoscopy or by laparotomy and tended to be of short duration (four months). Toxic effects of this therapy were similar to those observed in patients receiving LAK and IL-2 therapy systemically with the exception that our patients routinely developed diffuse abdominal swelling and rebound abdominal tenderness. LAK activity was not maintained in the peritoneal cavity unless interleukin-2 was administered concurrently. LAK activity was observed in the peritoneal cavity for a minimum of five consecutive days while IL-2 was being administered. Activity fell back to baseline approximately 48 hours after discontinuation of intraperitoneal infusions of IL-2. Gamma interferon levels rose appreciably in the peritoneal fluid and there was evidence from monocyte activation in vivo. Intraperitoneal fibrosis limited the delivery of therapy beyond approximately three cycles. We conclude that this therapy is effective in bringing about tumor responses and is reasonably well tolerated. However, fibrosis in the peritoneal cavity will ultimately prevent the effective delivery of this therapy.