Salup R R, Wiltrout R H
Cancer Res. 1986 Jul;46(7):3358-63.
We have used a transplantable experimental murine renal carcinoma (Renca) to evaluate the adjuvant immunotherapeutic potential of cytotoxic lymphocytes stimulated by in vitro incubation for 24 h with human recombinant interleukin 2 (rIL-2). The Renca tumor model is therapeutically challenging since, following intrarenal implant, it grows progressively with local invasion and development of spontaneous metastases in abdominal lymph nodes, lungs, and liver. Therefore, successful treatment requires control of both primary tumor, local and regional invasive growth, and systemic metastases. Our studies have shown that rIL-2-stimulated cytotoxic lymphocytes efficiently lyse Renca in vitro. Further, both doxorubicin hydrochloride and an active metabolite of cyclophosphamide also inhibited the growth of Renca in vitro. In vivo administration of doxorubicin hydrochloride, cyclophosphamide or rIL-2-stimulated cytotoxic lymphocytes and rIL-2 to mice bearing established Renca tumors (7-day disease) resulted in a significant (P less than 0.01) increase in short-term survivors (at 45 days), but only 17% cures. However, combination chemoimmunotherapy consisting of doxorubicin hydrochloride and rIL-2-stimulated cytotoxic lymphocytes plus rIL-2 results in the cure of 67% of mice bearing established Renca. These results demonstrate that chemotherapy and immunotherapy with adoptively transferred cytotoxic lymphocytes can function synergistically in the treatment of established murine renal carcinoma.
我们使用了一种可移植的实验性小鼠肾癌（Renca）来评估经体外与人重组白细胞介素2（rIL-2）孵育24小时刺激的细胞毒性淋巴细胞的辅助免疫治疗潜力。Renca肿瘤模型在治疗上具有挑战性，因为肾内植入后，它会逐渐生长，并伴有局部侵袭以及在腹部淋巴结、肺和肝脏中发生自发性转移。因此，成功的治疗需要控制原发性肿瘤、局部和区域侵袭性生长以及全身转移。我们的研究表明，rIL-2刺激的细胞毒性淋巴细胞在体外能有效裂解Renca。此外，盐酸多柔比星和环磷酰胺的一种活性代谢物在体外也能抑制Renca的生长。对已患有Renca肿瘤（病程7天）的小鼠体内给予盐酸多柔比星、环磷酰胺或rIL-2刺激的细胞毒性淋巴细胞及rIL-2，导致短期存活者（45天时）显著增加（P小于0.01），但仅有17%的治愈率。然而，由盐酸多柔比星和rIL-2刺激的细胞毒性淋巴细胞加rIL-2组成的联合化学免疫疗法可使67%已患有Renca的小鼠治愈。这些结果表明，化疗和采用过继转移细胞毒性淋巴细胞的免疫疗法在已患小鼠肾癌的治疗中可发挥协同作用。
