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-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. RESULTS: 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. CONCLUSIONS: Our results demonstrate that AGM-1470 is ineffective on lymphoid tumor cell proliferation and could potentially be safely administered to lymphoma patients.

Antibiotics, Antineoplastic↗

PubMedDate not supplied

[Study of human lymphocyte proliferation in vitro in response to tetanus toxoid].

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B-Lymphocytes↗

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Isolation of follicular dendritic cells from human tonsils and adenoids. VI. Analysis of prostaglandin secretion.

Follicular dendritic cells (FDC) are able to fix high amounts of immune complexes by C3b or Fc receptors without endocytosis and for long periods of time. In order to determine the function of this retention, we analysed the secretion of prostaglandin E2 (PGE2) by FDC in vitro; indeed, it is well-known that immune complex fixation on cells may induce PGE2 production. FDC were isolated by enzymic digestion of lymph follicles dissected under the biomicroscope from human tonsils or adenoids. Isolated FDC appeared as spherical clusters where they enveloped lymphoid cells with their cytoplasmic extensions. Tests were performed in synthetic culture media or in media supplemented with foetal calf serum. PGE2 production in FDC suspensions was compared to that of lymphocyte or macrophage-enriched populations prepared from the same human tonsils. In all experimental conditions, FDC and macrophage-enriched cell populations produced high levels of PGE2, inversely to lymphoid cell populations. This secretion was inhibited by indomethacin. At the ultrastructural level, we also showed that 3H-arachidonic acid was metabolized in cell membranes of all three cell types. The PGE2 produced in the culture media, according to our experimental conditions, do not influence cell proliferation, as assessed by 3H-thymidine incorporation tests on phytohaemagglutinin-stimulated lymphocytes.

Adenoids↗