Compositions and Methods for Treating Melanoma--Further Modifications

Unmet Need
Therapeutic cancer vaccines aim to activate the antitumor T cell response. These vaccines are designed to prime naïve antitumor T cells, by activating antigen presenting cells, particularly dendritic cells (DCs). DNA-based cancer vaccines are a particularly promising approach, partially due to the ease with which they can be manufactured. However, DNA-based cancer vaccines to date have been largely ineffective in the clinic.  This is attributed to the poor immunogenicity of DNA-based vaccines on their own. Consequently, there is a need to develop effective formulations and adjuvants that amplify the antitumor responses elicited by DNA-based cancer vaccines.
 
Technology Overview
The inventors have developed a novel approach to properly prime the immune response in a patient to tumor antigen. This approach combines a DNA-based vaccine, consisting of CCL20 (MIP-3α) fused to the tumor antigen, with the administration of type I interferon (IFN) and 5-aza-2’-deoxycitidine (AZA), and CpG. MIP-3α binds to CCR6, a chemokine receptor found on immature dendritic cells, thereby targeting the tumor antigen to dendritic cells. This approach reduces the tumor burden in melanoma mouse models. The addition of IFN, AZA, and CpG significantly enhanced the immunogenicity of this tumor vaccine, increasing the median survival of vaccine alone by 39% and no vaccine by 86%. Importantly, this system is able to change targeted antigens easily, allowing the use of different or multiple tumor antigens to personalize treatment options.  
 
Stage of Development
This was found to increase the immune response and median survival in mouse models of melanoma.
 
Publications
Gordy, JT et al. J Immunother. 2018 May. (41)4: 181-189.
 

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