Cancer vaccines containing cross-priming liposomes - from animal model to clinical trials
 
Dennis Christensen
Center for Vaccine Research, Statens Serum Institut, Denmark
Correspondence: DEN@SSI.DK
 
Immunotherapy is a promising tool for intervention but cancer vaccines based on polypeptides have so far had limited success because efficient cancer elimination requires potent CTLs and long-lived memory CD8+ T cells which is very difficult to achieve with subunit vaccine formulations. Aspects such as the internalization route, in vivo trafficking, and the simultaneous activation through pattern-recognition receptors have a determining influence in how antigens are handled for cross-presentation by DCs. We will here present work that exploit a PRR combination strategy to obtain a liposome formulation that promote strong CD8+ T-cell responses through efficient cross priming. Our lead candidate CAF09 is a liposomal formulation that exploits two ligands for TH17 responses and optimal cross priming of CD8 responses;  a C-type lectin-receptor ligand (monomycolate) and a TLR3 agonist, Poly(I:C). This adjuvant induces very high CD8+ T cell responses against a range of polypeptide based vaccines and has strong therapeutic efficacy in different cancer models in mice. Recent data from a malaria mouse model strictly dependent on CD8 responses to the P. falciparum CSP demonstrate that immunizations induce the development of strong CD8+ T-cell responses to CSP that inhibit parasite infection and confer sterilizing immunity.
The CAF09 formulation is now produced under GMP and for the first time now tested in a human clinical immunotherapy trial against prostate cancer in combination with the tumor associated antigen BCL-Xl.
I will present an update on the mechanism of action of CAF09 and the latest clinical trial status.