Adoptive cell therapy using PD-1+ myeloma-reactive T cells eliminates established myeloma in mice. J Immunother Cancer 2017;5:51
Date
06/24/2017Pubmed ID
28642819Pubmed Central ID
PMC5477110DOI
10.1186/s40425-017-0256-zScopus ID
2-s2.0-85021161579 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
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.
Author List
Jing W, Gershan JA, Blitzer GC, Palen K, Weber J, McOlash L, Riese M, Johnson BDAuthor
Bryon D. Johnson PhD Adjunct Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cell Line, Tumor
Cytokines
Immunologic Memory
Immunophenotyping
Immunotherapy, Adoptive
Lymphocyte Activation
Lymphocytes, Tumor-Infiltrating
Mice, Inbred C57BL
Multiple Myeloma
Programmed Cell Death 1 Receptor
T-Lymphocyte Subsets
Tumor Cells, Cultured
