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

Weiqing Jing, Jill A. Gershan, Grace C. Blitzer, Katie Palen, James Weber, Laura McOlash, Matthew Riese, Bryon D. Johnson

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.