Rituximab is a chimeric murine/human monoclonal antibody that binds to @entity2225 on B lymphocytes. Although binding of the Fab domain may induce apoptosis, the Fc domain recruits immune effector functions to mediate cell lysis. Interleukin-12 (IL-12) facilitates cytolytic T-cell responses, enhances the lytic activity of natural killer (NK) cells, and induces the secretion of @entity379 ) by both T and NK cells. Therefore, the hypothesis was considered that combining IL-12 with rituximab would augment the immune-mediated cell lysis induced by rituximab. A phase 1 study of IL-12 in combination with rituximab was conducted in 43 adults with @entity1892 to determine the optimal immunologic dose of this combination. @entity2408 was administered at a dose of 375 mg/m(2) by intravenous infusion weekly for 4 weeks, and IL-12 was given subcutaneously twice weekly. The starting dose of IL-12 was 30 ng/kg and this was escalated to 500 ng/kg. Constitutional symptoms and liver enzyme elevations at 500 ng/kg of IL-12 were dose limiting. A greater than 20-fold increase in the serum levels of @entity379 and a 2.5- to 5-fold increase in @entity371 ( @entity371 ) levels was seen at IL-12 doses of 100 ng/kg or greater. Objective responses occurred in 29 of the 43 @entity1 (69%), with 8 of 11 complete responses seen at IL-12 doses of 300 ng/kg or greater. The optimal immunologic dose of IL-12 in combination with rituximab was determined to be 300 ng/kg subcutaneously twice weekly starting on day 2. These data suggest that IL-12 and rituximab is an active combination and further studies of this combination in @entity1892 are warranted.

Phase 1 study of interleukin-12 in combination with rituximab in @entity1 with XXXX .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity2225 :: ('54474', 'Gene') :: ['CD20'] @entity1892 :: ('MESH:D016393', 'Disease') :: ['B-cell lymphoma', 'B-cell non-Hodgkin lymphoma'] @entity379 :: ('3458', 'Gene') :: ['interferon gamma (IFN-gamma', 'IFN-gamma'] @entity2408 :: ('CHEBI:64357', 'Chemical') :: ['Rituximab'] @entity371 :: ('3627', 'Gene') :: ['IP-10', 'inducible protein 10']
@entity1892 :: (MESH:D016393,Disease) :: ['B-cell non-Hodgkin lymphoma']
