The potent angioinhibin AGM-1470 stimulates normal but not human tumoral lymphocytes

Background: 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. Methods: The possible effect of AGM-1470 on the proliferation of normal or tumor lymphocytes was evaluated by thymidine-incorporation 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. Results: As shown previously, AGM-1470 stimulates the proliferation of normal B lymphocytes through an action on normal T cells. The angioinhibin was ineffective on the 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 cc-cultured with normal T lymphocytes were insensitive to the drug. Conclusions: Our results demonstrate that AGM-1470 is ineffective on lymphoid tumor cell proliferation and could potentially be safely administered to lymphoma patients.