一种用于治疗表达人HER2/neu的肿瘤的重组IgG3-(白细胞介素-2)融合蛋白。
A recombinant IgG3-(IL-2) fusion protein for the treatment of human HER2/neu expressing tumors.
作者信息
Penichet M L, Dela Cruz J S, Shin S U, Morrison S L
机构信息
Department of Microbiology and Molecular Genetics, and the Molecular Biology Institute, University of Califorina, Los Angeles, 405 Hilgard Avenue, Los Angeles, CA 90095-1489, USA.
出版信息
Hum Antibodies. 2001;10(1):43-9.
Anti-HER2/neu therapy of human HER2/neu expressing malignancies such as breast cancer has shown only partial success in clinical trials. To expand the clinical potential of this approach, we have genetically engineered an anti-HER2/neu human IgG3 fusion protein containing interleukin-2 (IL-2) fused at its carboxyl terminus. Anti-Her2/neu IgG3-(IL-2) retained antibody and cytokine related activity. Treatment of immunocompentent mice with this antibody fusion protein resulted in significant retardation in the subcutaneous (s.c.) growth of CT26-HER2/neu tumors suggesting that anti-HER2/neu IgG3-(IL-2) fusion protein will be useful in the treatment of HER2/neu expressing tumors. We also found that fusing IL-2 to human IgG3 results in a significant enhancement of the murine anti-human antibody (MAHA) response.
针对人类表达HER2/neu的恶性肿瘤（如乳腺癌）进行的抗HER2/neu治疗在临床试验中仅取得了部分成功。为了拓展这种治疗方法的临床潜力，我们通过基因工程构建了一种抗HER2/neu人IgG3融合蛋白，其羧基末端融合了白细胞介素-2（IL-2）。抗Her2/neu IgG3-(IL-2)保留了抗体和细胞因子相关活性。用这种抗体融合蛋白治疗免疫功能正常的小鼠，导致CT26-HER2/neu肿瘤的皮下（s.c.）生长显著减缓，这表明抗HER2/neu IgG3-(IL-2)融合蛋白将有助于治疗表达HER2/neu的肿瘤。我们还发现，将IL-2与人IgG3融合会显著增强小鼠抗人抗体（MAHA）反应。
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