Publication Date:
2009-11-20
Description:
Abstract 1216 Poster Board I-238 Background: PD-1 (Program Death-1), an immune inhibitory receptor and its ligands PD-L1 and PD-L2, participate in peripheral tolerance and play a key role in immune suppression and evasion mechanisms in cancer and chronic infectious diseases. PD-1 inhibits activation signals and functions as a pro-apoptotic receptor in effector lymphocytes, and consequently regulates the extent and duration of specific adaptive and innate immune responses. CT-011, a humanized antibody, blocks the function of PD-1, resulting in increased activities of T and NK cells in vitro and in enhanced tumor immunity in experimental tumor models. At the molecular level, the antibody enhances PI3K-mediated survival and trafficking signals, attenuates cell death in effector/memory (CD4+CD45RO+) cells, and enhances trafficking in response to Stromal Cell-derived Factor-1 (SDF-1). We hypothesized that CT-011 would enhance effector/memory cells in patients with DLBCL after AuSCT and delay recurrence. Methods: We treated 41 patients (pts) with DLBCL from 30-90 days after AuSCT with CT-011 and now report data on effector/memory and memory lymphocytes in the first 30 pts. CT-011 was given at a dose of 1.5mg/kg for 3 doses, 6 weeks apart. The primary endpoint was to determine the proportion of patients who have not relapsed or died within 18 months following autologous PBSCT, and it is too early for that analysis. Our secondary endpoint was to measure the number of effector /memory and memory lymphocytes before and after treatment, and those data are the subject of this report. Results: Flow cytometry analyses (Table) on pre (baseline: BL) and post-treatment blood samples from the first 30 pts enrolled show elevated levels of specific effector/memory and memory CD4+ T lymphocytes following treatment with CT-011; the median absolute number (ABS) of effector/memory CD4+CD45RO+CD62L-CCR7- cells was increased by +49% from BL (p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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