Schmiegel W, Schmielau J, Henne-Bruns D, Juhl H, Roeder C, Buggisch P, Onur A, Kremer B, Kalthoff H, Jensen E V
Medizinische Universitätsklinik, Knappschaftskrankenhaus, Ruhr-Universität Bochum, 44892 Bochum, Germany.
Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12622-6. doi: 10.1073/pnas.94.23.12622.
The increased expression of epidermal growth factor receptor induced by tumor necrosis factor alpha renders pancreatic cancer cells more susceptible to antibody-dependent cellular cytotoxicity by a mAb specific for this receptor. Laboratory studies with athymic mice bearing xenografts of human pancreatic cancer cells demonstrated a cytokine-induced ability of the mAb to cause significant tumor regression. In a phase I/II clinical trial, 26 patients with unresectable pancreatic cancer were enrolled into three cohorts receiving variable amounts of the antibody together with a constant amount of tumor necrosis factor alpha. With increasing doses of antibody, the growth of the primary tumor was significantly inhibited. This was reflected by a longer median survival, with one complete remission lasting for 3 years obtained with the highest dose of antibody employed. Thus, a combination of the cytokine, tumor necrosis factor alpha, with a mAb to the epidermal growth factor receptor offers a potentially useful approach for the treatment of pancreatic cancer.
肿瘤坏死因子α诱导的表皮生长因子受体表达增加，使胰腺癌细胞对一种针对该受体的单克隆抗体介导的抗体依赖性细胞毒性更敏感。用人胰腺癌细胞异种移植的无胸腺小鼠进行的实验室研究表明，该单克隆抗体具有细胞因子诱导的显著肿瘤消退能力。在一项I/II期临床试验中，26例不可切除胰腺癌患者被纳入三个队列，接受不同剂量的抗体以及恒定剂量的肿瘤坏死因子α。随着抗体剂量的增加，原发肿瘤的生长受到显著抑制。这表现为中位生存期延长，使用最高剂量抗体时获得了1例持续3年的完全缓解。因此，细胞因子肿瘤坏死因子α与表皮生长因子受体单克隆抗体联合使用，为胰腺癌治疗提供了一种潜在的有效方法。
