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通过与抗重组白细胞介素-2(rIL-2)的鼠单克隆抗体的F(ab')2片段形成免疫复合物来增强重组白细胞介素-2(rIL-2)的抗肿瘤活性。

Enhancement of the anti-tumor activity of recombinant interleukin-2 (rIL-2) by immunocomplexing with an F(ab')2 fragment of murine monoclonal antibody against rIL-2.

作者信息

Sato J, Hamaguchi N, Doken K, Gotoh K, Ootsu K, Iwasa S, Ogawa Y, Toguchi H

机构信息

DDS Research Laboratories, Chemical Industries, Ltd., Osaka, Japan.

出版信息

Biol Pharm Bull. 1994 Aug;17(8):1101-5. doi: 10.1248/bpb.17.1101.

Abstract

We have investigated the biological properties of an immune complex composed of recombinant interleukin-2 (rIL-2) and an F(ab')2 fragment of a monoclonal antibody against rIL-2 in mice for the induction of killer cells and anti-tumor activity, as well as the pharmacokinetic properties of the immune complex injected subcutaneously into mice. The immune complex demonstrated sustained serum rIL-2 levels, with a 2.4-times longer "mean-residence-time" than free rIL-2. A more significant portion of rIL-2 was detected in lymph nodes after the subcutaneous injection of the immune complex than with rIL-2 alone. Splenic lymphocytes from mice given the immune complex showed higher killer cell activity against YAC-1 and P815 cells than those from mice given rIL-2 alone. The immune complex also exerted a more significant anti-tumor effect in a dose-dependent manner in Meth-A fibrosarcoma-bearing mice than dit rIL-2 alone.

摘要

我们研究了由重组白细胞介素-2(rIL-2)和抗rIL-2单克隆抗体的F(ab')2片段组成的免疫复合物在小鼠体内诱导杀伤细胞和抗肿瘤活性的生物学特性,以及皮下注射到小鼠体内的该免疫复合物的药代动力学特性。该免疫复合物显示出持续的血清rIL-2水平,其“平均驻留时间”比游离rIL-2长2.4倍。皮下注射免疫复合物后,在淋巴结中检测到的rIL-2比例比单独注射rIL-2时更高。接受免疫复合物的小鼠的脾淋巴细胞对YAC-1和P815细胞的杀伤细胞活性高于单独接受rIL-2的小鼠。在携带Meth-A纤维肉瘤的小鼠中,该免疫复合物也比单独使用rIL-2以剂量依赖的方式发挥更显著的抗肿瘤作用。

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