Dinney C P, Utsugi T, Fidler I J, von Eschenbach A C, Killion J J
Department of Cell Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Cancer Res. 1992 Mar 1;52(5):1155-61.
The purpose of these experiments was to evaluate the possibility that the systemic administration of liposomes containing synthetic macrophage activation CGP 31362 or CGP 19835 in mice which were simultaneously receiving injections of gamma-interferon or interleukin 2 would lead to enhanced regression of spontaneous lung metastases produced by syngeneic renal adenocarcinoma. The kidneys of BALB/c mice were given injections of renal adenocarcinoma cells, and 10 days later the kidney with local tumor was surgically resected. These mice were then given injections i.v. with liposomes and with gamma-interferon (s.c.) or interleukin 2 (i.p.). Systemic administration of MLV-CGP 31362 and MLV-CGP 19835A significantly reduced the number of lung metastases in nephrectomized mice. Both lung tumor burden and regional recurrence were further reduced by the s.c. injection of gamma-interferon or i.p. injection of interleukin 2. Long-term survivors were observed only in the groups of animals treated with liposomes containing macrophage activators and with lymphokines. Evaluation of host responsiveness to this immunotherapy revealed in situ activation of alveolar macrophages by administration of MLV-CGP 31362 or MLV-CGP 19835A, which was enhanced in mice also treated with interleukin 2. Normal levels of natural killer cell activity were reduced in the spleens of tumor-bearing mice but were restored subsequent to treatment with MLV-CGP 31362. These results indicate the potential usefulness of treating metastatic renal cell carcinoma by systemic administration of liposomes containing synthetic macrophage activators in combination with parental injections of lymphokines.
这些实验的目的是评估在同时接受γ-干扰素或白细胞介素2注射的小鼠中，全身给予含有合成巨噬细胞激活剂CGP 31362或CGP 19835的脂质体是否会导致同基因肾腺癌产生的自发性肺转移瘤的消退增强。给BALB/c小鼠的肾脏注射肾腺癌细胞，10天后手术切除有局部肿瘤的肾脏。然后给这些小鼠静脉注射脂质体以及皮下注射γ-干扰素或腹腔注射白细胞介素2。全身给予MLV-CGP 31362和MLV-CGP 19835A可显著减少肾切除小鼠的肺转移瘤数量。皮下注射γ-干扰素或腹腔注射白细胞介素2可进一步降低肺肿瘤负荷和局部复发率。仅在接受含有巨噬细胞激活剂的脂质体和淋巴因子治疗的动物组中观察到长期存活者。对宿主对这种免疫疗法的反应性评估显示，给予MLV-CGP 31362或MLV-CGP 19835A可使肺泡巨噬细胞原位激活，在同时接受白细胞介素2治疗的小鼠中这种激活作用增强。荷瘤小鼠脾脏中的自然杀伤细胞活性正常水平降低，但在用MLV-CGP 31362治疗后恢复。这些结果表明，全身给予含有合成巨噬细胞激活剂的脂质体并联合注射淋巴因子治疗转移性肾细胞癌具有潜在的应用价值。
