Development of novel combined cancer immunotherapy using adoptive naive T cell transfer.

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In adoptive cell therapy(ACT), the intrinsic properties of the transferred cell population, particularly its state of differentiation, are considered to be crucial to the success of ACT based approaches, and naive T cells are ideal for ACT because of their in vivo persistence and high proliferative potential.In this study, we evaluated the synergic anti-tumor effect of CTLA-4 blockade combined with ACT considering the state of differentiation of transferred cells in mouse colon cancer model.CTLA-4 blockade combined with naive T-cell transfer showed the strongest antitumor effect among all groups. Moreover, CTLA-4 blockade can drive polarization of tumor-infiltrating T cells toward the T helper 1 lineage and suppress the frequency of Tregs within tumor especially in combination with naive T-cell transfer.These data support the notion that the combination of CTLA-4 blockade and ACT containing a lot of naive cells could expert powerful antitumor effects in clinical setting.