SELECTIVE INTERFERON-INDUCED ENHANCEMENT OF TUMOR-ASSOCIATED ANTIGENS ON A SPECTRUM OF FRESHLY ISOLATED HUMAN ADENOCARCINOMA CELLS

SELECTIVE INTERFERON-INDUCED ENHANCEMENT OF TUMOR-ASSOCIATED ANTIGENS ON A SPECTRUM OF FRESHLY ISOLATED HUMAN ADENOCARCINOMA CELLS
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DOI:
10.1093/jnci/81.7.502
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发表时间:
1989-04-05
影响因子:
10.3
通讯作者:
GREINER, JW
GREINER, JW
中科院分区:
医学1区
文献类型:
--
作者:
GUADAGNI, F;SCHLOM, J;GREINER, JW

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从细胞学诊断为腺癌(n = 43)、恶性非上皮性肿瘤(n = 10)、分析了肿瘤抗原TAG-72 [由单克隆抗体(MAb)B72.3识别]和癌胚抗原(CEA)组成性水平的表达(由MAb COL-4识别)以及I类和II类主要组织相容性(MHC)抗原,以及人干扰素(Hu-IFN)增强这些抗原的细胞表面表达的能力,如通过MAb结合所测量的。I型和II型IFN均增强TAG-72和CEA的表达,并改变MHC抗原的表达水平。三种不同Hu-IFN(IFN-α A、IFN-β ser和IFN-γ)的比较研究显示IFN-γ。在增强B72.3或COL-4结合方面是最有效的。与IFN-γ不同,介导的诱导II类人白细胞抗原,肿瘤抗原表达的变化包括增强的组成型抗原表达; TAG-72或CEA的从头诱导不能通过I型或II型IFN实现。在43个从不同腺癌患者分离的积液中,42个(97.7%)表达CEA或TAG-72,并且用Hu-IFN治疗增加了42个样品中的36个(85.7%)的任一抗原的表达水平。这些研究证明了通过Hu-IFN增强从浆液性渗出液分离的人癌细胞上的肿瘤相关抗原,其可用于增强缀合的MAb对人癌病变的靶向。
Freshly isolated cells from patients with pleural or peritoneal effusions cytologically diagnosed as adenocarcinoma (n = 43), malignant nonepithelial neoplasms (n = 10), and benign (n = 8) were analyzed for expression of constitutive levels of the tumor antigens TAG-72 [recognized by monoclonal antibody (MAb) B72.3] and carcinoembryonic antigen (CEA) (recognized by MAb COL-4) as well as the class I and class II major histocompatibility (MHC) antigens, and the ability of human interferons (Hu-IFNs) to enhance cell surface expression of those antigens as measured by MAb binding. Both type I and type II IFNs enhanced the expression of TAG-72 and CEA and altered the level of expression of the MHC antigen. Comparative studies of three different Hu-IFNs (IFN-.alpha.A, IFN-.beta.ser, and IFN-.gamma.) revealed that IFN-.gamma. was the most potent in augmenting either B72.3 or COL-4 binding. Unlike the IFN-.gamma.-mediated induction of the class II human leukocyte antigens, the change in tumor antigen expression consisted of enhanced constitutive antigen expression; de novo induction of either TAG-72 or CEA could not be achieved by either type I or type II IFN. Of 43 effusions isolated from different adenocarcinoma patients, 42 (97.7%) expressed either CEA or TAG-72, and treatment with Hu-IFN increased the level of expression of either antigen in 36 of 42 samples (85.7%). These studies demonstrate the augmentation of tumor-associated antigens on human carcinoma cells isolated from serous effusions by Hu-IFNs which may be used to enhance the targeting of conjugated MAbs to human carcinoma lesions.