Brooks Kimberly J, Coleman Elaine J, Vitetta Ellen S
Cancer Immunobiology Center and the Immunology Graduate Program, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Int J Cancer. 2008 Nov 15;123(10):2438-45. doi: 10.1002/ijc.23793.
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 of UV3 in several other CD54(+) epithelial tumors. A panel of 16 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.
我们之前描述过一种单克隆抗人CD54抗体(UV3)在移植了人多发性骨髓瘤、淋巴瘤和黑色素瘤细胞系的SCID小鼠中的研发和测试情况。在所有这3种情况下,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(细胞间黏附分子-1)在许多不同类型的癌细胞上上调,我们现在研究了UV3在其他几种CD54阳性上皮性肿瘤中的抗肿瘤活性。检测了一组16种人乳腺癌、前列腺癌、非小细胞肺癌和胰腺肿瘤细胞系与UV3的反应性,其中13种呈阳性。将每种癌症的代表性CD54阳性细胞系皮下接种到SCID小鼠体内。一旦肿瘤形成,就使用不同的剂量方案给予UV3。UV3减缓了所有4种肿瘤的生长,尽管它不能治愈肿瘤。当将UV3或吉西他滨给予移植了非小细胞肺癌细胞系或胰腺肿瘤细胞系的SCID小鼠时,UV3与单独化疗的效果相同。当同时给予吉西他滨和UV3时,观察到了最佳的抗肿瘤反应。UV3已被人源化(cUV3),计划进行毒理学研究和临床试验,以评估cUV3在患有这些肿瘤中的一种或多种的患者中的安全性和活性。