Gillies S D, Reilly E B, Lo K M, Reisfeld R A
Research Department, Abbott Biotech, Inc., Needham Heights, MA 02194.
Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1428-32. doi: 10.1073/pnas.89.4.1428.
A genetically engineered fusion protein consisting of a chimeric anti-ganglioside GD2 antibody (ch14.18) and interleukin 2 (IL2) was tested for its ability to enhance the killing of autologous GD2-expressing melanoma target cells by a tumor-infiltrating lymphocyte line (660 TIL). The fusion of IL2 to the carboxyl terminus of the immunoglobulin heavy chain did not reduce IL2 activity as measured in a standard proliferation assay using either mouse or human T-cell lines. Antigen-binding activity was greater than that of the native chimeric antibody. The ability of resting 660 TIL cells to kill their autologous GD2-positive target cells was enhanced if the target cells were first coated with the fusion protein. This stimulation of killing was greater than that of uncoated cells in the presence of equivalent or higher concentrations of free IL2. Such antibody-cytokine fusion proteins may prove useful in targeting the biological effect of IL2 and other cytokines to tumor cells and in this way stimulate their immune destruction.
一种由嵌合抗神经节苷脂GD2抗体（ch14.18）和白细胞介素2（IL2）组成的基因工程融合蛋白，对其增强肿瘤浸润淋巴细胞系（660 TIL）杀伤表达自体GD2的黑色素瘤靶细胞的能力进行了测试。在使用小鼠或人T细胞系的标准增殖试验中，IL2与免疫球蛋白重链羧基末端的融合并未降低IL2活性。抗原结合活性高于天然嵌合抗体。如果先用融合蛋白包被靶细胞，静息的660 TIL细胞杀伤其自体GD2阳性靶细胞的能力会增强。在存在等量或更高浓度游离IL2的情况下，这种杀伤刺激作用大于未包被细胞。这种抗体-细胞因子融合蛋白可能被证明可用于将IL2和其他细胞因子的生物学效应靶向肿瘤细胞，从而刺激对肿瘤细胞的免疫破坏。
