rituximab

Rituximab inhibits the proliferation of stimulated human B cells, which is associated with a relative increase of B cells with an activated naive phenotype. Aside from this population shift, there are no major changes in phenotype or cytokine profile of the various B-cell subsets. B cells stimulated in the presence of rituximab induces stronger T-cell proliferation, compared to B cells stimulated in the absence of rituximab. All lymphoma cells tested are equally sensitive to antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-mediated phagocytosis of tumor cells, and rituximab-induced apoptosis. Rituximab induces high CDC killing of follicular lymphoma cells.

Cell Assay: A single injection of rituximab or the murine anti-CD20 Ab 1F5, given i.p. 1 day after the tumor, cures 100% of the animals. Depletion of either NK cells or neutrophils or both in tumor-injected animals does not affect the therapeutic activity of the drug. Similarly, rituximab is able to eradicate tumor cells in athymic nude mice, suggesting that its activity is T cell independent.

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Animal Studies: C57BL/6 mice (8-10 wk of age) are inoculated 8x103 EL4-CD20+ cells in 200 uL of saline by tail vein injection. In parallel groups of mice, 150 g of rituximab, murine anti-CD20 IgG2a Ab 1F5, or control anti-human IL-2R Ab daclizumab in 300 uL of saline, or saline only is inoculated i.p. 24 h later.