Nomi S, Naito K, Kahan B D, Pellis N R
Cancer Res. 1986 Nov;46(11):5606-10.
Augmentation of specific chemoimmunotherapy by daily, intrasplenic injection of interleukin-2 (IL-2) was assessed in a methylcholanthrene (MCA)-induced fibrosarcoma model in C3H/HeJ mice. Daily access to the spleen was achieved by relocating the organ into the subcutis while leaving its blood supply intact. Following intrasplenic injection of 80 units of human IL-2 into MCA-F tumor-bearing mice for 6 days, spleen cells tested in the local adoptive transfer assay showed specific neutralization of MCA-F, but not the antigenically different MCA-D, tumor. Depletion of the spleen cell population with monoclonal antibodies and complement showed that the responding cell bore the surface markers Thy 1.2 and Lyt 2. Mice bearing established MCA-F tumors underwent a variety of chemoimmunotherapy regimens, including 1 microgram of 1-butanol, extracted isoelectrophoretically purified tumor-specific transplantation antigen, a single i.p. dose of cyclophosphamide (20 mg/kg), and/or either i.p. or intrasplenic injection of 80 units of IL-2. Specific triple chemoimmunotherapy including daily intrasplenic IL-2, but not i.p., administration was superior in the degree of tumor neutralization to all single or double therapy protocols. Furthermore, the combined triple modality inhibited spontaneous lung colonization by clone 9-4, a highly metastatic variant of MCA-F; both the numbers of lung colonies (median, 17; range, 2 to 55, versus median, 3, range, 0 to 42; P less than 0.005) and the incidence were decreased. The combined treatment group displayed 35% of hosts free of lung metastasis, while 100% of the control animals had lung colonies (P less than 0.02). Thus antitumor immunity was augmented in vivo using IL-2 delivered by intrasplenic, but not i.p., injection. Furthermore, chemoimmunotherapy including intrasplenic IL-2 injection potentiated the antitumor immunity achieved with combined tumor-specific transplantation antigen and cyclophosphamide.
在C3H/HeJ小鼠的甲基胆蒽（MCA）诱导的纤维肉瘤模型中，评估了通过每日脾内注射白细胞介素-2（IL-2）增强特异性化学免疫疗法的效果。通过将脾脏重新安置到皮下同时保持其血液供应完整，实现了每日对脾脏的接触。在携带MCA-F肿瘤的小鼠中，每日脾内注射80单位人IL-2，持续6天，在局部过继转移试验中测试的脾细胞显示出对MCA-F的特异性中和作用，但对抗抗原性不同的MCA-D肿瘤没有作用。用单克隆抗体和补体耗尽脾细胞群体表明，反应细胞带有表面标志物Thy 1.2和Lyt 2。携带已建立的MCA-F肿瘤的小鼠接受了各种化学免疫疗法方案，包括1微克经等电聚焦纯化的肿瘤特异性移植抗原（从1-丁醇提取物中获得）、单次腹腔注射环磷酰胺（20毫克/千克），和/或腹腔内或脾内注射80单位IL-2。包括每日脾内注射IL-2（而非腹腔内注射）的特异性三联化学免疫疗法在肿瘤中和程度上优于所有单一或双重治疗方案。此外，联合三联疗法抑制了MCA-F的高转移变体克隆9-4的自发性肺定植；肺集落数量（中位数，17；范围，2至55，相比之下，中位数，3，范围，0至42；P小于0.005）和发生率均降低。联合治疗组显示35%的宿主没有肺转移，而100%的对照动物有肺集落（P小于0.02）。因此，通过脾内注射而非腹腔内注射IL-2在体内增强了抗肿瘤免疫力。此外，包括脾内注射IL-2的化学免疫疗法增强了联合肿瘤特异性移植抗原和环磷酰胺所实现的抗肿瘤免疫力。
