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使用放射性标记单克隆抗体在体内对肿瘤反应性淋巴结淋巴细胞进行定位

Localization of tumor-reactive lymph node lymphocytes in vivo using radiolabeled monoclonal antibody.

作者信息

Triozzi P L, Kim J A, Aldrich W, Young D C, Sampsel J W, Martin E W

机构信息

Department of Medicine, Ohio State University Comprehensive Cancer Center/Arthur G. James Cancer Hospital and Research Institute, Columbus.

出版信息

Cancer. 1994 Feb 1;73(3):580-9. doi: 10.1002/1097-0142(19940201)73:3<580::aid-cncr2820730314>3.0.co;2-b.

DOI:10.1002/1097-0142(19940201)73:3<580::aid-cncr2820730314>3.0.co;2-b
PMID:8299079
Abstract

BACKGROUND

Lymph node lymphocytes vary in their responsiveness to tumor. A technique has been developed that uses radiolabeled monoclonal antibody (MoAb) against the tumor-associated mucin, TAG-72, and a gamma-detecting probe by which lymph nodes containing microscopic tumor and/or shed TAG-72 can be identified in vivo. The immunologic characteristics of these lymph nodes were examined.

METHODS

Patients with colon cancer received 125I-labeled MoAb CC49 by intravenous injection preoperatively. During laparotomy lymph nodes that appeared normal on inspection and palpation but which contained radiolabeled MoAb were identified using a hand-held gamma-detecting probe. These lymph nodes and other lymph node and tumor specimens were resected for analysis.

RESULTS

Lymph nodes identified by the probe were found by immunohistochemical studies to contain microscopic tumor and/or shed antigen associated with germinal centers. They were characterized by greater CD4+:CD8+ ratios, rates of expansion, and cytolytic activity compared with lymphocytes from lymph nodes with macroscopic tumor, noninvolved lymph nodes, and tumors. All lymph node lymphocytes identified by the probe demonstrated significant proliferative responses to autologous tumor and, in contrast to lymphocytes from noninvolved lymph nodes, significant proliferative responses to allogeneic TAG-72+ tumor cells and to soluble TAG-72+ mucin.

CONCLUSIONS

By locating lymph nodes with microscopic tumor and/or shed antigen, the use of radiolabeled MoAb in vivo can be used to reproducibly identify tumor-reactive lymph node lymphocytes. This technique may be useful in identifying cells for use in adoptive immunotherapy programs and in studying the regulation of immune responses in vivo.

摘要

背景

淋巴结淋巴细胞对肿瘤的反应性各不相同。已开发出一种技术,该技术使用针对肿瘤相关粘蛋白TAG-72的放射性标记单克隆抗体(MoAb)和γ检测探针,通过该探针可在体内识别含有微小肿瘤和/或脱落TAG-72的淋巴结。对这些淋巴结的免疫特性进行了检查。

方法

结肠癌患者术前静脉注射125I标记的MoAb CC49。在剖腹手术期间,使用手持式γ检测探针识别那些在检查和触诊时看似正常但含有放射性标记MoAb的淋巴结。切除这些淋巴结以及其他淋巴结和肿瘤标本进行分析。

结果

通过免疫组织化学研究发现,探针识别出的淋巴结含有微小肿瘤和/或与生发中心相关的脱落抗原。与来自有肉眼可见肿瘤的淋巴结、未受累淋巴结和肿瘤的淋巴细胞相比,它们的特征是CD4 +:CD8 +比值更高、扩增率更高和细胞溶解活性更高。探针识别出的所有淋巴结淋巴细胞对自体肿瘤均表现出显著的增殖反应,并且与来自未受累淋巴结的淋巴细胞不同,对同种异体TAG-72 +肿瘤细胞和可溶性TAG-72 +粘蛋白也表现出显著的增殖反应。

结论

通过定位含有微小肿瘤和/或脱落抗原的淋巴结,体内使用放射性标记的MoAb可用于重复性地识别肿瘤反应性淋巴结淋巴细胞。该技术可能有助于识别用于过继性免疫治疗方案的细胞,并有助于研究体内免疫反应的调节。

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