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第二代抗癌胚抗原单克隆抗体的特性分析

Characterization of second-generation monoclonal antibodies against carcinoembryonic antigen.

作者信息

Hansen H J, Goldenberg D M, Newman E S, Grebenau R, Sharkey R M

机构信息

Immunomedics, Inc., Morris Plains, New Jersey, 07103.

出版信息

Cancer. 1993 Jun 1;71(11):3478-85. doi: 10.1002/1097-0142(19930601)71:11<3478::aid-cncr2820711104>3.0.co;2-a.

Abstract

BACKGROUND

A second-generation panel of anti-carcinoembryonic antigen (CEA) monoclonal antibodies (MoAb) has been generated, and the specificity has been compared with that of the first panel of MoAb used to differentiate meconium antigen (MA) from CEA.

METHODS AND RESULTS

Four of the MoAb had similar specificities to the first-generation panel of NP MoAb. MN-15, like its first-generation equivalent, NP-1, reacts with normal cross-reactive antigen (NCA), MA, and CEA; both MN-15 and NP-1 react strongly with granulocytes. MN-2 has properties similar to Class II NP-2, being reactive with MA and CEA, cross-blocking binding to CEA by NP-1, and having low reactivity with granulocytes; both NP-2 and MN-2 stain granulocytes in frozen tissue sections but show minimal staining of granulocytes in sections fixed in formaldehyde solution and embedded in Paraplast (Fischer Scientific, Pittsburgh, PA). MN-14 demonstrates properties similar to the Class III anti-CEA-specific MoAb, NP-4, being unreactive with NCA and MA. MN-14, as compared with NP-4, demonstrated significantly superior tumor targeting in a human colon tumor xenograft model and consistently stronger staining of frozen sections of colon cancer. A fifth MoAb, MN-3, had properties uniquely different from the NP series of MoAb, reacting strongly with granulocytes but not demonstrating the liquid-phase ion-sensitivity binding of CEA exhibited by MN-15 and NP-1.

CONCLUSIONS

MN-14 is being evaluated for radioimmunodetection of and radioimmunotherapy for CEA-containing cancers, whereas MN-3 is being studied for the radioimmunodetection of occult infections and sites of inflammation.

摘要

背景

已制备出第二代抗癌胚抗原(CEA)单克隆抗体(MoAb)面板,并将其特异性与用于区分胎粪抗原(MA)和CEA的第一代MoAb面板进行了比较。

方法与结果

其中四种MoAb与第一代NP MoAb面板具有相似的特异性。MN-15与其第一代等效物NP-1一样,可与正常交叉反应抗原(NCA)、MA和CEA发生反应;MN-15和NP-1均与粒细胞强烈反应。MN-2具有与II类NP-2相似的特性,可与MA和CEA发生反应,通过NP-1交叉阻断与CEA的结合,并且与粒细胞的反应性较低;NP-2和MN-2均可对冷冻组织切片中的粒细胞进行染色,但在甲醛溶液固定并包埋在Paraplast(Fischer Scientific,匹兹堡,宾夕法尼亚州)中的切片中,粒细胞的染色极少。MN-14表现出与III类抗CEA特异性MoAb NP-4相似的特性,与NCA和MA无反应。与NP-4相比,MN-14在人结肠肿瘤异种移植模型中表现出明显更好的肿瘤靶向性,并且对结肠癌冷冻切片的染色始终更强。第五种MoAb MN-3具有与NP系列MoAb独特不同的特性,与粒细胞强烈反应,但未表现出MN-15和NP-1所具有的CEA液相离子敏感性结合。

结论

MN-14正在用于含CEA癌症的放射免疫检测和放射免疫治疗的评估,而MN-3正在用于隐匿性感染和炎症部位的放射免疫检测研究。

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