Adoptive cell therapy using PD-1 + myeloma-reactive T cells eliminates established myeloma in mice

• Published in: Journal for immunotherapy of cancer Vol. 5; no. 1; p. 51
• Main Authors: Jing, Weiqing, Gershan, Jill A, Blitzer, Grace C, Palen, Katie, Weber, James, McOlash, Laura, Riese, Matthew, Johnson, Bryon D
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 20-06-2017; BMJ Publishing Group LTD; BioMed Central; BMJ Publishing Group
• Subjects: Adoptive cell therapy; Analysis; Animals; Antibodies; Antigens; Bone marrow; Cancer; Cancer therapies; Cancer-infiltrating lymphocytes; Care and treatment; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - transplantation; Cell Line, Tumor; Cellular therapy; Chemotherapy; Cloning; Cytokines; Cytokines - biosynthesis; Diagnosis; Flow cytometry; Hematopoietic stem cells; Immunologic Memory - immunology; Immunophenotyping; Immunotherapy; Immunotherapy, Adoptive - methods; Laboratories; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes, Tumor-Infiltrating - immunology; Melanoma; Mice, Inbred C57BL; Multiple myeloma; Multiple Myeloma - immunology; Multiple Myeloma - therapy; Myeloma; PD-1; PD-L1; Peptides; Programmed Cell Death 1 Receptor - blood; Software; T cells; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - transplantation; Transplantation; Tumor Cells, Cultured; Tumor necrosis factor-TNF; Tumors; Vaccines; PD-L1; Adoptive cell therapy; Myeloma; PD-1; Cancer-infiltrating lymphocytes
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1186/s40425-017-0256-z

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.
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.
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.
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.