Anti-cancer vaccines and related therapy
The present invention provides an anti-cancer vaccine comprising: (i) at least one peptide comprising the amino acid sequence of a neoantigen encoded by a mutant homologous recombination (HR) DNA repair gene selected from the group: BRCA1, BRCA2, PALB2, CDK12, RAD51B, RAD51C and RAD51D, wherein the mutant gene comprises a reversion mutation; and/or (ii) at least one polynucleotide encoding the at least one peptide of (i). Also provided are engineered T cells that recognise said neoantigen. Related methods and medical uses of the vaccine and/or engineered T cell are provided, including for the treatment of cancers, such as homologous recombination (HR) deficient cancers that acquire PARP inhibitor resistance or platinum resistance by development of reversion mutations in an HR DNA repair gene selected from the group: BRCA1, BRCA2, PALB2, CDK12, RAD51B, RAD51C and RAD51D.
1 . An anti-cancer vaccine comprising:
(i) at least one peptide comprising the amino acid sequence of SEQ ID NO: 934; and/or
(ii) at least one polynucleotide encoding the at least one peptide of (i).
2 . The anti-cancer vaccine of claim 1 , wherein the vaccine comprises a DNA or RNA sequence encoding said peptide.
3 . The anti-cancer vaccine of claim 2 , wherein the DNA or RNA sequence is provided in the form of a viral vector.
4 . The anti-cancer vaccine of claim 3 , wherein the viral vector is an oncolytic virus.
5 . The anti-cancer vaccine of claim 1 , wherein said vaccine is in the form of a plurality of dendritic cells (DCs) that have been pulsed with said at least one peptide and which are capable of presenting said peptide to one or more T cells when administered to a subject.
6 . The anti-cancer vaccine of claim 1 , wherein the vaccine comprises 2, 3, 4, 5, 6, 7, 8, 9, 10 or more different neoantigens and/or polynucleotide encoding the different neoantigens.
7 . The anti-cancer vaccine of claim 1 , further comprising at least one adjuvant.
8 . The anti-cancer vaccine of claim 7 , wherein said at least one adjuvant is selected from: a toll-like receptor (TLR) agonist.
9 . The anti-cancer vaccine of claim 1 , wherein the vaccine is in the form of or in conjunction with a nanoparticle.