Courtney L P, Phelps J L, Karavodin L M
Hybritech Incorporated, San Diego, CA 92196-9006.
Immunopharmacology. 1994 Nov-Dec;28(3):223-32. doi: 10.1016/0162-3109(94)90058-2.
We examined the ability of anti-human recombinant interleukin-2 (hu rIL-2) monoclonal antibody DMS-1.10 to increase serum half-life of hu rIL-2, and the effect of this complex on inhibition of tumor progression in a B16-F10 murine melanoma model. In C57B1/6 mice, intravenous (i.v.) injection of DMS-1.10 premixed with 1 x 10(4) units (U) of hu rIL-2 at a 1:1 molar ratio extended serum half-life greater than 10-fold (222 min) when compared to the same dose of hu rIL-2 alone (20 min). In a murine tumor model, multiple intraperitoneal (i.p.) injections of non-neutralizing DMS-1.10 premixed with hu rIL-2 at a 5:1 molar ratio reduced the growth rate of subcutaneous (s.c.) B16-F10 tumor in C57B1/6 mice by 64% when compared to PBS and irrelevant antibody treated controls. Although similar treatment with hu rIL-2 alone reduced tumor growth rate by 46%, it was significantly less effective than the premixed treatment. Results from a flow cytometry assay confirm B16-F10 does not have IL-2 receptors, precluding direct inhibition of tumor growth by hu rIL-2 treatments. We propose that therapeutic efficacy of hu rIL-2 is improved by prolonging the in vivo half-life with an anti-IL-2 antibody, thus augmenting hu rIL-2 bioactivity and enhancing the hosts immune response against tumor.
我们研究了抗人重组白细胞介素-2（hu rIL-2）单克隆抗体DMS-1.10延长hu rIL-2血清半衰期的能力，以及该复合物在B16-F10小鼠黑色素瘤模型中对抑制肿瘤进展的影响。在C57B1/6小鼠中，静脉注射（i.v.）以1:1摩尔比与1×10⁴单位（U）hu rIL-2预混合的DMS-1.10，与单独注射相同剂量的hu rIL-2（20分钟）相比，血清半衰期延长了10倍以上（222分钟）。在小鼠肿瘤模型中，以5:1摩尔比将非中和性DMS-1.10与hu rIL-2预混合后多次腹腔注射（i.p.），与用PBS和无关抗体处理的对照组相比，C57B1/6小鼠皮下（s.c.）B16-F10肿瘤的生长速率降低了64%。虽然单独用hu rIL-2进行类似处理可使肿瘤生长速率降低46%，但其效果明显不如预混合处理。流式细胞术检测结果证实B16-F10没有IL-2受体，排除了hu rIL-2处理直接抑制肿瘤生长的可能性。我们提出，通过用抗IL-2抗体延长体内半衰期来提高hu rIL-2的治疗效果，从而增强hu rIL-2的生物活性并增强宿主对肿瘤的免疫反应。
