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J Immunother. 2011 Jun;34(5):409-18. doi: 10.1097/CJI.0b013e31821ca6ce.

PD-1 blockade by CT-011, anti-PD-1 antibody, enhances ex vivo T-cell responses to autologous dendritic cell/myeloma fusion vaccine.

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1
Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. jrosenb1@bidmc.harvard.edu

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 with a control population of normal volunteers, increased PD-1 expression was observed on T cells isolated from patients with myeloma. It is interesting to note that after 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 compared with 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 after DC/tumor fusion stimulation.

PMID:
21577144
PMCID:
PMC3142955
DOI:
10.1097/CJI.0b013e31821ca6ce
[Indexed for MEDLINE]
Free PMC Article

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