CANCER VACCINE

1 - 34 . (canceled)

35 . A combination of a TLR-9 agonist and a conjugate of Formula (I) or pharmaceutically acceptable salt thereof,

wherein:

A is a self-immolative linker group;

D is selected from the group consisting of:

wherein * denotes a point of attachment of group D to group A;

R 15 is a side chain of one of the following amino acids: L-lysine, L-citrulline, L-arginine, L-glutamine or L-threonine;

R 16 is a side chain of a hydrophobic amino acid;

R 19 is an alkylene group;

R 32 is an alkylene group or an O-alkylene group wherein the O is attached to the carbonyl group of D2;

E is selected from the group consisting of:

wherein * denotes a point of attachment of group E to group D;

R 20 is H or lower alkyl;

R 21 is an alkylene group;

g is 0 when R 20 is H or g is 1 when R 20 is lower alkyl;

provided that E is E18 only when D is D1, D2 or D3 and provided that E is E1, E2, E3, E4, E5, E6, E7, E8, E9, E10, E11, E12, E13, E15, E20, E21, E93, E94 or E96 only when D is D1, D2, D3 or D4; and provided that E is E91, E92 or E95 only when D is D5 and provided that E is E97 only when D is D2;

G is absent or G is an amino acid sequence of up to 6 amino acids, attached through its N-terminus to group E and through its C-terminus to group J;

J is a peptide antigen, optionally substituted at its N and/or C-termini with up to 6 amino acids selected from the group of natural flanking residues for the antigen, and optionally terminated with NH 2 at the C-terminus so as to provide a C-terminal amide, and attached to group G through its N-terminus or, wherein G is absent, attached to group E through its N-terminus;

R 4 is CH 3 , CH 2 OH, CH 2 OCOR 11 , CH 2 OR 11 , CH 2 OSO 3 H, CH 2 SH, CH 2 SR 11 , CH 2 SOR 11 , CH 2 SO 2 R 11 , CH 2 PO 3 H 2 , CH 2 OP(O)(OH) 2 , CH 2 OP(O)(OH)(OR 11 ), CH 2 OP(O)(OR 11 ) 2 , CO 2 H, CH 2 NHCOR 11 , CH 2 NHCO 2 R 11 , CH 2 NHCONH 2 , CH 2 NHCONHR 11 , CH 2 NHCON(R 11 ) 2 , CH 2 N(R 11 ) 2 , CH 2 NHSO 2 R 11 ;

R 6 is OR 12 , OH or H;

R 7 is OR 12 , OH or H; provided that at least one of R 6 and R 7 is OR 12 ; wherein when R 6 is OR 12 , R 7 is H, R 8 is C 1 -C 15 alkyl;

denotes an optional double bond linking the carbon adjacent to R 7 with the carbon adjacent to R 8 ;

R 8 is H or C 1 -C 15 alkyl having a straight or branched carbon chain, wherein the carbon chain optionally incorporates one or more double bonds, one or more triple bonds, one or more oxygen atoms and/or a terminal or non-terminal optionally substituted aryl group;

R 11 is lower alkyl, lower alkenyl or aralkyl;

R 12 is C 6 -C 30 acyl having a straight or branched carbon chain optionally substituted with one or more hydroxy groups at positions 2 and/or 3 of the acyl group and/or an optionally substituted chain terminating aryl group and which optionally incorporates one or more double bonds, one or more triple bonds, and/or one or more optionally substituted arylene groups and wherein the carbon chain is optionally substituted with one or more deuterium atoms; wherein the optional substituents on the aryl and arylene groups may be selected from halogen, cyano, dialkylamino, C 1 -C 6 amide, nitro, C 1 -C 6 alkoxy, C 1 -C 6 acyloxy and C 1 -C 6 thioalkyl.

36 . The combination according to claim 35 wherein A is selected from the group consisting of:

wherein * denotes a point of attachment of group A to group D;

each Q 1 , the same or different, is independently selected from the group consisting of H, alkyl, alkoxy, halogen, nitro, aryl; or, together with the ring to which it is attached, forms a fused bicyclic aryl group;

p is an integer from 1 to 4;

Alk 1 is C 1 -C 4 straight chain alkyl; and

R 29 is H or lower alkyl;

provided that A is A1 only when D is D1 and provided that A is A2 only when D is D2, D3 or D5 and provided that A is A3 only when D is D1, D3 or D4 and provided that A is A4 only when D is D2, D3 or D5.

37 . The combination according to claim 35 wherein R 15 is the side chain of L-citrulline or L-alanine.

38 . The combination according to claim 36 , wherein R 16 is a side chain of one of an amino acid selected from: L-phenylalanine, L-valine, L-leucine, L-isoleucine, L-norleucine, L-methionine, L-tryptophan or L-tyrosine.

39 . The combination according to claim 36 wherein D is D2 and R 32 is (C 6 -C 8 )-alkylene.

40 . The combination according to claim 35 wherein E is selected from the group consisting of E3, E4, E93, E94 and E97.

41 . The combination according to claim 35 wherein G is selected from the group consisting of FFRK, GFLG and FKRL.

42 . The combination according to claim 35 wherein R 4 is CH 2 OH.

43 . The combination according to claim 35 wherein R 6 is OH.

44 . The combination according to claim 35 wherein R 7 is OR 12 .

45 . The combination according to claim 44 wherein R 12 is C 6 -C 30 acyl having a straight carbon chain containing no double bonds, triple bonds, oxygen atoms, aryl groups and which is unsubstituted or substituted with a terminating aryl group.

46 . The combination according to claim 45 wherein R 12 is C 18 -C 26 acyl having a straight carbon chain containing no double bonds, triple bonds, oxygen atoms, aryl groups and which is unsubstituted.

47 . The combination according to claim 35 wherein R 8 is C 1 -C 15 alkyl.

48 . The combination according to claim 47 wherein R 8 is C 10 to C 14 alkyl having a straight or branched carbon chain containing no double bonds, triple bonds, oxygen atoms or aryl groups.

49 . The combination according to claim 35 wherein J is a peptide antigen from a tumour, virus or bacteria.

50 . The combination according to claim 35 wherein the TLR-9 agonist is a CpG oligodeoxynucleotide.

51 . The combination according to claim 50 wherein the TLR-9 agonist is an oligodeoxynucleotide comprising a core sequence comprising a hexamer with a central unmethylated cytosine-phosphate-guanine (CpG) moiety, having a general formula RRCGYY; wherein R represents a purine; C represents a cytosine; G represents a guanine; and Y a pyrimidine.

52 . The combination according to claim 51 wherein the TLR-9 agonist is an unmethylated single-stranded CpG oligodeoxynucleotide of about 15 to about 30 bases.

53 . A pharmaceutical composition comprising a combination according to claim 35 and a pharmaceutically acceptable carrier or excipient.

54 . A method of treating cancer in a subject, the method comprising administering to the subject a therapeutically effective amount of the combination of claim 35 , wherein the combination is administered by intratumoural or peritumoural injection to a cancerous tumour.