Brent Hanks, MD, PhD
Metabolic re-programming of dendritic cell-based cancer vaccines.
Dendritic cells are potent antigen presenting cells capable of stimulating tumor immunity. Despite their promise as vectors for cancer vaccines, limited clinical efficacy has been observed to date. We have identified a fundamental metabolic pathway that is triggered within the melanoma microenvironment and that results in the potent suppression of dendritic cell function.
After identifying a fatty acid transporter as playing a critical role in this pathway, we have determined that the pharmacological inhibition of this transporter is capable of reversing this process of dendritic cell tolerization and significantly enhancing T cell activation. Based on these findings, we now propose to engineer a dendritic cell-based cancer vaccine that has been genetically silenced for this transporter and to test the impact of this modification both in a transgenic melanoma model as well as in advanced melanoma patients who are refractory to checkpoint inhibitor immunotherapy. In addition to generating more potent ex vivo DC-based vaccines, this work is aimed at validating this recently identified fatty acid transporter as a genetic target for future in vivo DC-targeted treatment strategies.
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“Cancers have a devastating impact on patients and their families. But given the science and technology that’s understood and available these days, which was nonexistent just 10 years ago, there’s a lot of reason to be hopeful about future outcomes for cancer patients. There are still barriers to be overcome, but significant steps forward have already been realized in gene therapy and immunology, and many more untapped ideas and promising opportunities await exploration. I feel optimistic.”