Antoine N, Daukandt M, Locigno R, Heinen E, Simar L J, Castronovo V
Metastasis Research Laboratory, University of Liège, Belgium.
Tumori. 1996 Jan-Feb;82(1):27-30. doi: 10.1177/030089169608200105.
AGM-1470 is a newly synthesized molecule developed as an analog of the potent anti-angiogenic fumagillin. Its efficacy in restraining tumor growth in vivo and the absence of major side effects have already led to phase I clinical trials in patients with solid cancers. However, neither the exact mechanisms of action of AGM-1470 nor its effects on the host of normal cells have been extensively studied. Recently, we showed that AGM-1470 enhanced the proliferation of B lymphocytes in the presence of T cells. Since AGM-1470 could potentially be used in patients with lymphoma, it was urgent to test the effect of the molecule on the proliferation of tumor lymphocytes.
The possible effect of AGM-1470 on the proliferation of normal or tumor lymphocytes was evaluated by thymidine-incorporated assays. Normal T and B lymphocytes were purified from human tonsils. The tumor lymphocytes used in the study were Molt 3, Molt 4 and Jurkatt cell lines for the T lineage and Daudi and Radji cell lines for the B lineage.
As shown previously, AGM-1470 stimulates the proliferation of normal B lymphocytes through an action on normal T cells. THe angioinhibin was ineffective ont eh proliferation of both T and B transformed cells. Moreover, in the presence of the drug, tumor T cells co-cultured with normal B lymphocytes did not induce any increase in B cell proliferation, as previously observed with normal T lymphocytes. Inversely, tumor B cells co-cultured with normal T lymphocytes were insensitive to the drug.
Our results demonstrate that AGM-1470 is ineffective on lymphoid tumor cell proliferation and could potentially be safely administered to lymphoma patients.
AGM - 1470是一种新合成的分子，作为强效抗血管生成烟曲霉素的类似物而研发。其在体内抑制肿瘤生长的功效以及缺乏主要副作用已促使其进入实体癌患者的I期临床试验。然而，AGM - 1470的确切作用机制及其对正常细胞宿主的影响尚未得到广泛研究。最近，我们发现AGM - 1470在有T细胞存在的情况下可增强B淋巴细胞的增殖。由于AGM - 1470可能用于淋巴瘤患者，因此迫切需要测试该分子对肿瘤淋巴细胞增殖的影响。
通过掺入胸苷的试验评估AGM - 1470对正常或肿瘤淋巴细胞增殖的可能影响。从人扁桃体中纯化正常T和B淋巴细胞。研究中使用的肿瘤淋巴细胞为T谱系的Molt 3、Molt 4和Jurkatt细胞系以及B谱系的Daudi和Radji细胞系。
如先前所示，AGM - 1470通过作用于正常T细胞刺激正常B淋巴细胞的增殖。血管抑制素对T和B转化细胞的增殖均无效。此外，在药物存在的情况下，与正常B淋巴细胞共培养的肿瘤T细胞并未像先前观察到的正常T淋巴细胞那样诱导B细胞增殖增加。相反，与正常T淋巴细胞共培养的肿瘤B细胞对该药物不敏感。
我们的结果表明，AGM - 1470对淋巴瘤细胞增殖无效，并且有可能安全地给予淋巴瘤患者。
