The antitumor activity of an anti-CD54 antibody in SCID mice xenografted with human breast, prostate, non-small cell lung, and pancreatic tumor cell lines

The antitumor activity of an anti-CD54 antibody in SCID mice xenografted with human breast, prostate, non-small cell lung, and pancreatic tumor cell lines
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DOI:
10.1002/ijc.23793
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发表时间:
2008-11-15
影响因子:
6.4
通讯作者:
Vitetta, Ellen S.
Vitetta, Ellen S.
中科院分区:
医学1区
文献类型:
--
作者:
Brooks, Kimberly. L.;Coleman, Elaine J.;Vitetta, Ellen S.

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我们之前已经描述了在移植了人类多发性骨髓瘤、淋巴瘤和黑色素瘤细胞系的SCID小鼠中开发和测试单克隆抗人CD54抗体(UV3)。在所有3例病例中,UV3在减缓肿瘤生长和/或延长生存期方面都非常有效。由于CD54(ICAM-1)在许多不同类型的癌细胞上被上调,我们现在研究了其他几种CD54(+)上皮肿瘤的抗肿瘤活性或UV3。我们检测了1例人乳腺、前列腺、非小细胞(NSC)肺和胰腺肿瘤细胞系UV3的反应性,其中13例呈阳性。在SCID小鼠皮下培养来自每种癌症的具有代表性的CD54+细胞系。一旦肿瘤形成。UV3使用不同的剂量方案。UV3减缓了所有4个肿瘤的生长,尽管它没有治愈。当将UV3或吉西他滨应用于移植了NSC肺肿瘤细胞系或胰腺肿瘤细胞系的SCID小鼠时,UV3与单独化疗一样有效。当吉西他滨和UV3联合使用时,观察到最佳的抗肿瘤反应。UV3已被嵌合(cUV3),毒理学研究和临床试验正在计划中,以评估cUV3在一种或多种肿瘤患者中的安全性和活性。(C) 2008 Wiley-Liss。公司。
We have previously described the development and testing of a monoclonal anti-human CD54 antibody (UV3) in SCID mice xenografted with human multiple myeloma, lymphoma, and melanoma cell lines. In all 3 cases, UV3 was highly effective at slowing the growth of tumors and/or prolonging survival. Since CD54 (ICAM-1) is up-regulated on many different types of cancer cells, we have now investigated the anti-tumor activity or UV3 in several other CD54(+) epithelial tumors. A panel of I human breast, prostate, non-small cell (NSC) lung, and pancreatic tumor cell lines was examined for reactivity with UV3, and 13 were positive. A representative CD54+ cell line from each cancer was grown subcutaneously in SCID mice. Once the tumors were established. UV3 was administered using different dose regimens. UV3 slowed the growth of all 4 tumors, although it was not curative. When UV3 or gemcitabine were administered to SCID mice xenografted with a NSC lung tumor cell line or a pancreatic tumor cell line, UV3 was as effective as the chemotherapy alone. When gemcitabine and UV3 were administered together, the best anti-tumor responses were observed. UV3 has been chimerized (cUV3) and both toxicology studies and clinical trials are planned to assess the safety and activity of cUV3 in patients with one or more of these tumors. (C) 2008 Wiley-Liss. Inc.