Chu F.-L.,Nanomedicine Engineering Research Center in Suzhou |
Westin J.R.,Nanomedicine Engineering Research Center in Suzhou |
Zhang M.,Nanomedicine Engineering Research Center in Suzhou |
Jing Y.,Nanomedicine Engineering Research Center in Suzhou |
And 7 more authors.
Journal of Leukemia and Lymphoma | Year: 2013
Objective A phase II trial of anti- programmed death-1(PD-1) monoclonal antibody CT-011, an anti PD-l humanized monoclonal antibody combined with rituximab therapy in patients with relapsed follicular lymphoma (FL) were conducted. Methods In order to evaluate the safety and efficacy of CT-011, the impacts of CT-011 on immune cells both from the peripheral blood (PB) samples and tumor microenvironment were examined. PB and core needle biopsies from involved lymph nodes were collected prior to and on day 14 after the first infusion of CT-011. PB mononuclear cells (PBMC) were analyzed by multiparametric flow cytometry to determine various immune cell subsets. Whole genome gene expression profiling (GEP) was performed on core needle biopsies. Results A significant increase in the absolute number of PB immune cells were observed in day 14 samples compared with baseline including total lymphocyte count (P < 0.01), CD+ 3 T cells (P = 0.01), CD+ 4 T cells (P < 0.01). Comparison of GEP from core needle biopsies obtained pretreatment and day 14 (n = 8 pairs) showed up regulation of several genes associated with T cell activation. Conclusion Administration of CT-011 was associated with increase in the numbers of CD+ 4 T cells and resulted in activation of T cells in the PB and the tumor microenvironment in FL. These results provide insight into the mechanism of action of CT-011 and offer a predictive biomarker for selection of patients for future clinical trials with this class of agents in FL.