Mellstedt H, Fagerberg J, Frödin J E, Hjelm-Skog A L, Liljefors M, Markovic K, Mosolits S, Ragnhammar P
Cancer Centre Karolinska, Department of Oncology, Karolinska Hospital/Karolinska Institute, Stockholm, Sweden.
Ann N Y Acad Sci. 2000 Jun;910:254-61; discussion 261-2. doi: 10.1111/j.1749-6632.2000.tb06713.x.
GA733/EpCAM is an oncofetal antigen abundantly expressed in colorectal carcinoma. This antigen can spontaneously induce a humoral and cellular antitumor immunity and may therefore be a suitable target structure for immunotherapy. Patients with advanced colorectal carcinoma have been treated with monoclonal antibodies (MAb17-1A) against this structure. The data indicate that the chimeric variant was not superior to the original mouse MAb. Addition of cytokines and chemotherapeutics may improve the therapeutic effect of the MAb. A particularly interesting regimen is a combination of MAb17-1A/GM-CSF/alpha-IFN/5-Fu. The GA733 protein antigen can also be used as a vaccine. Patients with colorectal carcinoma stages B and C were vaccinated with this protein antigen in combination with GM-CSF as an adjuvant cytokine. A strong type I T cell response was induced that seemed to be MHC class I as well as class II restricted. No systemic side effects were noted.
GA733/EpCAM是一种在结直肠癌中大量表达的癌胚抗原。该抗原可自发诱导体液和细胞抗肿瘤免疫，因此可能是免疫治疗的合适靶结构。晚期结直肠癌患者已接受针对该结构的单克隆抗体（MAb17-1A）治疗。数据表明，嵌合变体并不优于原始小鼠单克隆抗体。添加细胞因子和化疗药物可能会提高单克隆抗体的治疗效果。一种特别有趣的方案是MAb17-1A/GM-CSF/α-干扰素/5-氟尿嘧啶联合使用。GA733蛋白抗原也可作为疫苗使用。B期和C期结直肠癌患者接种了这种蛋白抗原，并联合GM-CSF作为辅助细胞因子。诱导了强烈的I型T细胞反应，该反应似乎受MHC I类以及II类限制。未观察到全身副作用。
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