UC San Diego

Therapeutic cancer vaccination strategies aim to stimulate patient’s immune system to combat disease. Approaches to generating cancer vaccines include utilizing autologous tumor cells and tumor-antigen loaded autologous dendritic cells. Recent studies demonstrate the potential to directly convert somatic cells of one lineage into others, a process called transdifferentiation. Here, we show the potential of utilizing this transdifferentiation process to convert cancer cell lines into myeloid-like cells by ectopic expression of two transcription factors, PU.1 and C/EBPα. The ectopic expression of these two transcription factors induce the expression of surface proteins characteristic of myeloid cells and these transdifferentiated cells acquired the potential to mount a partial inflammatory response to proinflammatory stimuli. Moreover, these transdifferentiated cancer cells generally lose their ability to form tumors in immune

competent mice but fail to control parental cell line tumor growth. Mice that developed tumors from the transdifferentiated cells were able to control the progression of parental cell lines better than those that had rejected the transdifferentiated cells. These findings highlight the potential of directly converting cancer cells into antigen-presenting cells as a potential therapeutic vaccination strategy for cancer.