Optimizing cell therapy against tumors is a balancing ACT
Adoptive cell transfer (ACT) therapy is used to treat patients with metastatic solid tumors. ACT involves the removal of some of the patient's cancer cells, and some of their immune T cells. When the cells are mixed together, specific parts of the cancer cells that stimulate the T cells to cause an immune attack can be identified. The T cells get expanded and re-infused into the patient to mount an immunological, anti-cancer response against the tumors. One of the challenges faced is selecting the appropriate T cells with proper antigen specificity.
In a new study appearing in the June 1 print issue of The Journal of Clinical Investigation, Nicholas Restifo and colleagues identified which cells are optimal for treating large, vascularized, established tumors. The authors use a mouse model that mimics the human clinical situation. They find that phenotypic and functional qualities of T cells are associated with the ability of ACT to cause regression of large, established melanomas. Seemingly paradoxical, nave and early effector T cells are more effective for tumor treatment than more differentiated T cells.
In an accompanying commentary, Daniel Speiser and Pedro Romero write, "optimal therapeutic efficacy may depend on different T cell selection and preparation strategies" and these findings indicate that a pragmatic strategy for ACT is to keep the in vitro T cell expansion phase as short as possible to keep them nave. These findings are important for development of improved adoptive immunotherapy approaches for treating tumors and established infectious diseases.
TITLE: Acquisition of full effector function in vitro paradoxically impairs the in vivo anti-tumor efficacy of adoptively transferred CD8+ T cells
Nicholas P. Restifo
NIH - National Cancer Institute, Bethesda, MD USA
Contact: Stacie Bloom
Journal of Clinical Investigation