Sabzevari H, Gillies S D, Mueller B M, Pancook J D, Reisfeld R A
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.
Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9626-30. doi: 10.1073/pnas.91.20.9626.
A genetically engineered fusion protein consisting of a human/mouse chimeric anti-ganglioside GD2 antibody (ch14.18) and recombinant human interleukin 2 (rhIL-2) was tested for its ability to target rhIL-2 to tumor sites and stimulate immune effector cells sufficiently to achieve effective tumor cell lysis in vivo. The ch14.18-IL-2 fusion protein proved more effective than equivalent doses of rhIL-2 in suppressing dissemination and growth of human neuroblastoma in an experimental hepatic metastases model of scid (severe combined immunodeficiency) mice reconstituted with human lymphokine-activated killer cells. The ch14.18-IL-2 fusion protein was also more proficient than equivalent doses of rhIL-2 in prolonging the life-span of these animals. This recombinant antibody-cytokine fusion protein may prove useful for future treatment of GD2-expressing human tumors in an adjuvant setting.
一种由人/鼠嵌合抗神经节苷脂GD2抗体（ch14.18）和重组人白细胞介素2（rhIL-2）组成的基因工程融合蛋白，对其将rhIL-2靶向肿瘤部位并充分刺激免疫效应细胞以在体内实现有效肿瘤细胞裂解的能力进行了测试。在用人淋巴因子激活的杀伤细胞重建的scid（严重联合免疫缺陷）小鼠的实验性肝转移模型中，ch14.18-IL-2融合蛋白在抑制人神经母细胞瘤的扩散和生长方面比等量的rhIL-2更有效。ch14.18-IL-2融合蛋白在延长这些动物的寿命方面也比等量的rhIL-2更有效。这种重组抗体-细胞因子融合蛋白可能对未来在辅助治疗中治疗表达GD2的人类肿瘤有用。
