CT-011 (anti PD-1antibody)

J Immunother. 2011 June; 34(5): 409–418. doi: 10.1097/CJI.0b013e31821ca6ce PMCID: PMC3142955 NIHMSID: NIHMS292929 PD-1 blockade by CT-011, anti PD-1 antibody, enhances ex-vivo T cell responses to autologous dendritic/myeloma fusion vaccine Jacalyn Rosenblatt, MD,1 Brett Glotzbecker, MD,1 Heidi Mills,1 Baldev Vasir, PhD,2 Dimitrios Tzachanis, MD/PhD,1 James D. Levine, MD,1 Robin M. Joyce, MD,1 Kerry Wellenstein,1 Whitney Keefe,1 Michael Schickler, PhD,3 Rinat Rotem-Yehudar, PhD,3 Donald Kufe, MD,2 and David Avigan, MD1 Author information ► Copyright and License information ► The publisher's final edited version of this article is available at J Immunother See other articles in PMC that cite the published article. Go to: Abstract We have developed a cancer vaccine in which autologous tumor is fused with dendritic cells (DCs) resulting in the presentation of tumor antigens in the context of DC mediated costimulation. In clinical trials, immunologic responses have been observed, however responses may be muted by inhibitory pathways. The PD1/PDL1 pathway is an important element contributing to tumor mediated immune suppression. In this study, we demonstrate that myeloma cells and DC/tumor fusions strongly express PD-L1. Compared to a control population of normal volunteers, increased PD-1 expression was observed on T cells isolated from patients with myeloma. Interestingly, following autologous transplantation, T cell expression of PD-1 returned to levels seen in normal controls. We examined the effect of PD-1 blockade on T cell response to DC/tumor fusions ex-vivo. Presence of CT-011, an anti-PD1 antibody, promoted the vaccine induced T cell polarization towards an activated phenotype expressing Th1 as compared to Th2 cytokines. A concomitant decrease in regulatory T cells and enhanced killing in a cytotoxicity assay was observed. In summary, we demonstrate that PD-1 expression is increased in T cells of patients with active myeloma, and that CT-011 enhances activated T cell responses following DC/tumor fusion stimulation.