Combination of vaccination and inhibition of MHC class I restricted antigen presentation
The present invention relates to a vaccine/inhibitor combination comprising as a vaccine at least one antigen and as an inhibitor at least one inhibitor of the major histocompatibility complex (MHC) class I restricted antigen presentation. The present invention furthermore relates to a method of vaccination of a mammal using the inventive vaccine/inhibitor combination. The present invention also provides kit of parts comprising the inventive vaccine/inhibitor combination, preferably in different parts of the kit, e.g. for prior, concurrent or subsequent administration of the different parts. Additionally the invention relates to a pharmaceutical composition comprising the inventive vaccine/inhibitor combination to further improve the immune response against tumour cells and infected cells having lost the capability of MHC class I restricted antigen presentation.
1. A kit of parts, the kit comprising:
(a) a pharmaceutical composition comprising an mRNA encoding a tumor cell antigen that is expressed in a cancer, wherein the antigen does not comprise an MHC class I heavy chain or β2m fusion protein, wherein the mRNA's coding sequence comprises a G/C content that is increased relative to a wild type coding sequence; and
(b) a pharmaceutical composition comprising an mRNA encoding a TAP inhibitor, wherein the mRNA's coding sequence comprises a G/C content that is increased relative to a wild type coding sequence,
wherein the pharmaceutical compositions of (a) and (b) are provided as separate components of the kit, wherein the pharmaceutical composition of (a) and (b) are both formulated for parenteral administration to a patient.
2. The kit of claim 1 , comprising a pharmaceutical composition comprising an additional antigen.
3. The kit of claim 1 , wherein the mRNA encoding the TAP inhibitor encodes the UL49.5 polypeptide.
4. The kit of claim 1 , wherein at least a portion of the mRNA encoding the antigen is complexed with a cationic component.
5. The kit of claim 4 , wherein the cationic component is a cationic polypeptide.
6. The kit of claim 4 , wherein the cationic component is protamine.
7. The kit of claim 4 , wherein the cationic component is a cationic lipid.
8. The kit of claim 1 , wherein the mRNA comprises a 5′UTR, 3′UTR, Poly-A tail and/or a Poly-C tail.
9. The kit of claim 1 , wherein the mRNA comprises a cap.
10. The kit of claim 1 , wherein the mRNA is a codon optimized mRNA.