Although treatment regimens involving the infusion of tumor-reactive T cells into patients with skin cancer (melanoma) have shown clinical benefit, there is plenty of room to improve the protocols to increase therapeutic benefit. Regimens currently being investigated in humans involve pre-treatment with agents that transiently decrease the number of immune cells (and that are known as nonmyeloablative agents), enabling the subsequently infused tumor-reactive T cells to increase in number in vivo.
In a study that appears in the February issue of the Journal of Clinical Investigation, Nicholas Restifo and colleagues from the National Institutes of Health show that in mice, pre-treatment with more intense immune cell--depleting strategies (known as myeloablative strategies) and a hematopoietic stem cell (HSC) transplantation enabled infused tumor-reactive CD8+ T cells to increase in number more than pre-treatment with nonmyeloablative agents.
Importantly, this increased expansion of the CD8+ T cell population correlated with increased tumor regression. Further analysis showed that it was the HSC transplantation, and not the increased immune cell depletion, that made the myeloablative agents more effective at inducing the infused tumor-reactive T cell population to expand and that it was the effector CD8+ T cell population, rather than the naïve T cell population, that expanded. This study has important implications for the future development of treatment regimens involving the infusion of tumor-reactive T cells into patients with melanoma.
In an accompanying commentary, Claudio Anasetti and James J. Mulé from the H. Lee Moffitt Comprehensive Cancer Center, Tampa, discuss the issues that are raised by these data and the implications that these issues have for the development of cell-based immunotherapies for cancer.
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