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

• Main Authors: Weiqing Jing, Jill A. Gershan, Grace C. Blitzer, Katie Palen, James Weber, Laura McOlash, Matthew Riese, Bryon D. Johnson
• Format: Article
• Language: English
• Published: BMJ Publishing Group 2017-06-01
• Series: Journal for ImmunoTherapy of Cancer
• Subjects: Myeloma; Adoptive cell therapy; PD-1; PD-L1; Cancer-infiltrating lymphocytes
• Online Access: http://link.springer.com/article/10.1186/s40425-017-0256-z

Abstract 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.