RT Journal Article
SR Electronic
T1 Adoptive cell therapy using PD-1<sup>+</sup> myeloma-reactive T cells eliminates established myeloma in mice
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP 51
DO 10.1186/s40425-017-0256-z
VO 5
IS 1
A1 Weiqing Jing
A1 Jill A. Gershan
A1 Grace C. Blitzer
A1 Katie Palen
A1 James Weber
A1 Laura McOlash
A1 Matthew Riese
A1 Bryon D. Johnson
YR 2017
UL http://jitc.bmj.com/content/5/1/51.abstract
AB Background Adoptive cellular therapy (ACT) with cancer antigen-reactive T cells following lymphodepletive pre-conditioning has emerged as a potentially curative therapy for patients with advanced cancers. However, identification and enrichment of appropriate T cell subsets for cancer eradication remains a major challenge for hematologic cancers.Methods PD-1+ and PD-1− T cell subsets from myeloma-bearing mice were sorted and analyzed for myeloma reactivity in vitro. In addition, the T cells were activated and expanded in culture and given to syngeneic myeloma-bearing mice as ACT.Results Myeloma-reactive T cells were enriched in the PD-1+ cell subset. Similar results were also observed in a mouse AML model. PD-1+ T cells from myeloma-bearing mice were found to be functional, they could be activated and expanded ex vivo, and they maintained their anti-myeloma reactivity after expansion. Adoptive transfer of ex vivo-expanded PD-1+ T cells together with a PD-L1 blocking antibody eliminated established myeloma in Rag-deficient mice. Both CD8 and CD4 T cell subsets were important for eradicating myeloma. Adoptively transferred PD-1+ T cells persisted in recipient mice and were able to mount an adaptive memory immune response.Conclusions These results demonstrate that PD-1 is a biomarker for functional myeloma-specific T cells, and that activated and expanded PD-1+ T cells can be effective as ACT for myeloma. Furthermore, this strategy could be useful for treating other hematologic cancers.Abbreviations:ACTAdoptive cell therapyCIITAClass II transactivatorMBMyeloma-bearingOVAOvalbuminPD-1Programmed death receptor-1PD-L1Programmed death receptor ligand-1SIYSIYRYYGLTILsTumor-infiltration lymphocytesWBIWhole body irradiation