While vaccination has become one of the most powerful weapons to fight a plethora of diseases, it has so far failed in cancer therapy. This fact is mostly attributed to the immune suppressive microenvironment of solid tumors. Therefore, scientists have learned over the years that in tumor immune therapy the abolishment of immune tolerance is maybe even more important than the vaccination itself.<br/>Therefore we report on PeptoMicelles tackeling immune tolerance by local delivery of inhibitors interphering with cAMP mediated immune suppression of regulatory T-cells. This therapeutic approach leads already to a reduced tumor growth without additional therapeutic intervention. If additionally a PeptoBrush based vaccine (antigen, immune activator and aDEC205 antibody are combined on cylindrical polymer brushed based on Polypept(o)ides) is applied, the full recression of the B16 melanoma can be observed in mice.<br/>On the other hand, the first cationic lipid based mRNA vaccine is currently in clinical phase I trails (BioNTech, Mainz) and demonstrated therapeutic effects after systemic application in mice and men, which underlines the potential of mRNA vaccines. In this respect, we develop Polypept(o)ide based mRNA polyplexes. Interestingly, the mRNA polyplexes are cross-linked by disulfide bonds and thus are stable in human serum avoiding aggregation of serum proteins, while efficiently transfecting murine or human bone marrow derived dendritic cells.<br/>We report on the progress of the introduced immune therapies and combinations thereoff.

Polypept(o)ide based tumor immune therapy: Combining vaccination and abolishment of immune tolerance

253rd National Meeting (2017)

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