| abstract |
Described herein is the identification of miRNAs (miRs) that are up-regulated in Th1 cells compared to Th2 cells (referred to herein as Th1-associated miRs). In particular, the miR-17-92 gene cluster was found to exhibit significantly greater expression in Th1 cells. Over-expression of miR-17-92 in T cells promotes the Th1 phenotype. Thus, the use of Th1-associated miRs for cancer immunotherapy is described. Provided herein are isolated T cells containing a heterologous nucleic acid molecule encoding a Th1-associated miR, such as the miR17-92 gene cluster, or a portion thereof. In some embodiments, the T cell is a tumor antigen (TA)-specific T cell, such as a TA-specific CTL. Further provided is a method of treating cancer in a subject by selecting a subject with cancer and administering to the subject an isolated T cell as disclosed herein. Also provided is a method of treating a subject with cancer by transfecting isolated T cells obtained from the subject with a heterologous nucleic acid molecule encoding a Th1-associated miR and administering the transfected T cells to the subject. In some embodiments of the method, the heterologous nucleic acid molecule encodes the miR-17-92 transcript or a portion thereof. In some embodiments, the isolated T cell is a TA-specific T cell, such as a CTL. |