Shetye J, Frödin J E, Christensson B, Grant C, Jacobsson B, Sundelius S, Sylvén M, Biberfeld P, Mellstedt H
Department of Pathology, Karolinska Institute and Hospital, Stockholm, Sweden.
Cancer Immunol Immunother. 1988;27(2):154-62. doi: 10.1007/BF00200021.
A therapeutic trial using repeated doses of a mouse monoclonal antibody against the tumor-associated antigen (TAA) CO17-1A in metastatic colorectal carcinomas was carried out. Metastatic lesions sampled by repeated thick needle (1.2 mm) biopsies during therapy were examined immunohistochemically for the presence of various TAAs, mouse IgG, complement, and infiltrating leukocytes. The CO17-1A was consistently expressed in all cases along the basement membrane of tumor glands and could only be demonstrated on cryostat sections whereas the TAAs GICA19-9, GA73-3, and Br55-2 were also visualized in B5-fixed paraffin-embedded biopsies. The CO17-1A and GA73-3 were predominantly present at the basal region in contrast to the GICA 19-9 and Br55-2 which were predominant at the luminal and the apical region of the tumor glands. Antigenic modulation was not seen either after 24-72 h or during prolonged treatment. In all cases the infused mouse IgG was detected, from 24 h after infusion up to 6-8 weeks, mainly along the basal region of tumor glands. In 13/14 posttreatment biopsies, complement factor C3 was found at the same sites as mouse IgG. In 6 out of 9 posttreatment biopsies an increase in mononuclear cells (monocytes, natural killer (NK) cells and/or T cells) was observed. Monocytes were close to the tumor cells whereas NK cells and T cells were predominantly scattered in the stroma.
开展了一项治疗试验，使用针对肿瘤相关抗原（TAA）CO17-1A的小鼠单克隆抗体重复给药治疗转移性结直肠癌。在治疗期间，通过重复粗针（1.2毫米）活检获取转移性病变样本，对其进行免疫组织化学检查，以检测各种TAA、小鼠IgG、补体和浸润白细胞的存在情况。CO17-1A在所有病例中均沿肿瘤腺管基底膜持续表达，且仅在低温恒温器切片上可见，而TAA GICA19-9、GA73-3和Br55-2在B5固定的石蜡包埋活检样本中也能显示。与主要位于肿瘤腺管腔面和顶端区域的GICA 19-9和Br55-2不同，CO17-1A和GA73-3主要存在于基底区域。在24至72小时后或长期治疗期间均未观察到抗原调制现象。在所有病例中，从输注后24小时直至6至8周，均可检测到输注的小鼠IgG，主要沿肿瘤腺管基底区域分布。在14份治疗后活检样本中的13份中，在与小鼠IgG相同的部位发现了补体因子C3。在9份治疗后活检样本中的6份中，观察到单核细胞（单核细胞、自然杀伤（NK）细胞和/或T细胞）增多。单核细胞靠近肿瘤细胞，而NK细胞和T细胞主要散布在基质中。
