UNASSIGNED: 2569 Background: Emerging clinical evidence suggests that @entity1568 -containing @entity171 such as @entity4381 have direct and indirect anticancer effects including immunomodulatory effects via activation of y   T cells. This phase I/II study evaluated the safety, pharmacodynamics and antitumor activity of @entity4381 in combination with low-dose @entity1199 in adults with advanced @entity5 . METHODS: We examined the effect of adding low-dose @entity1199 (2 x 10(6) IU/m(2) subcutaneously days 1 to 6) to @entity4381 (4mg intravenously day 1) in twenty-one @entity1 with different @entity5 (renal cell carcinoma= @entity1358 ; @entity3052 = @entity3052 ). RESULTS: A total of 58 treatment cycles of @entity4381 and low-dose @entity1199 were administered and the median number of treatment cycles was 2.7 (range 1-6). The regimen was well tolerated, with no grade 3-4 drug-related adverse events except for fever. Two @entity1 with @entity3052 (25 %) achieved objective @entity5 responses (partial remission). No objective responses were observed in both cohorts of @entity5 ( @entity1358 and MM), but four @entity1 @entity66 stabilization (SD) during treatment. Pharmacodynamic analyses showed significant in vivo activation ( @entity379 production) and expansion of y   T cells in all evaluable @entity1 . High pretreatment serum @entity7 levels and an unexpected increase of @entity7 induced by @entity4381 plus low-dose @entity1199 were correlated with lack of clinical response. CONCLUSIONS: This phase I/II trial suggests that @entity1583 are more susceptible to @entity5520 -mediated immunological antitumor effects than @entity5 and immunotherapy-induced @entity7 was identified as a new biomarker counteracting potential antitumor effects.

Pro- versus antitumor effects of XXXX -activated y   T cells in @entity5 immunotherapy.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity1568 :: ('MESH:D009584', 'Chemical') :: ['nitrogen'] @entity171 :: ('MESH:D004164', 'Chemical') :: ['bisphosphonates'] @entity66 :: ('MESH:D004194', 'Disease') :: ['achieved disease'] @entity7 :: ('7422', 'Gene') :: ['VEGF'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'solid tumors', 'malignancies'] @entity3052 :: ('MESH:D015470', 'Disease') :: ['malignant melanoma=MM and acute myeloid leukemia', 'AML'] @entity5520 :: ('D004164', 'Chemical') :: ['bisphosphonate'] @entity1358 :: ('MESH:D002292', 'Disease') :: ['RCC'] @entity379 :: ('3458', 'Gene') :: ['IFN-y'] @entity1583 :: ('MESH:D019337', 'Disease') :: ['hematologic malignancies'] @entity1199 :: ('3558', 'Gene') :: ['interleukin-2'] @entity4381 :: ('MESH:C088658', 'Chemical') :: ['zoledronic acid']
@entity5520 :: (D004164,Chemical) :: ['bisphosphonate']
