MODULATION OF NKT CELL ACTIVITY WITH ANTIGEN-LOADED CD1d MOLECULES

Patent metadata

Field	Value
Publication number	US-2017312356-A1
Application number	US-201715428106-A
Country	US
Kind code	A1
Filing date	Feb 8, 2017
Priority date	Feb 21, 2007
Publication date	Nov 2, 2017
Grant date	—

Abstract

The invention is directed to methods of modulating an immune response in an animal, comprising administering a composition comprising one or more soluble CD1d complexes, in particular non-specific soluble CD1d complexes. Soluble CD1d complexes comprise a soluble CD1d polypeptide, a β2-microglobulin polypeptide, and a ceramide-like glycolipid antigen bound to the CD1d antigen binding groove, and in certain embodiments, an immunogen. The administration of compositions of the present invention affects the activity of CD1d-restricted NKT cells, and in particular, allows for multiple administrations without causing CD1d-restricted NKT cell anergy.

First claim

1 - 77 . (canceled)

78 . A* composition comprising:
(a) an immunogen; (b) a CD1d complex, said complex comprising:
(i) an isolated soluble CD1d polypeptide sufficient to associate with β2-microglobulin and bind a ceramide-like glycolipid antigen;
(ii) an isolated polypeptide comprising β2-microglobulin or a fragment thereof associated with said CD1d polypeptide; and
(iii) a ceramide-like glycolipid antigen bound to said CD1d polypeptide; and
(c) a carrier.

79 . The composition of claim 78 , wherein the composition additionally comprises an adjuvant.

80 . The composition of claim 79 , wherein the adjuvant is a TLR agonist selected from the group consisting of: MPL, CpG, and BCG.

81 . The composition of claim 80 , wherein the adjuvant is MPL.

82 . The composition of claim 78 , wherein the ceramide-like glycolipid antigen comprises an α-galactosylceramide.

83 . The composition of claim 78 , wherein the soluble CD1d polypeptide comprises an amino acid sequence at least 90% identical to amino acids 21 to 295 of SEQ ID NO: 1.

84 . The composition of claim 78 , wherein the soluble CD1d polypeptide comprises an amino acid sequence at least 95% identical to amino acids 21 to 295 of SEQ ID NO: 1.

85 . The composition of claim 78 , wherein the soluble CD1d polypeptide comprises amino acids 21 to 295 of SEQ ID NO: 1.

86 . The composition of claim 78 , wherein the soluble CD1d polypeptide comprises amino acids 1 to 295 of SEQ ID NO: 1.

87 . The composition of claim 78 , wherein the soluble CD1d polypeptide comprises amino acids 20 to 295 of SEQ ID NO: 1, except for at least one but less than 10 conservative amino acid substitutions.

88 . The composition of claim 78 , wherein the soluble CD1d polypeptide further comprises a heterologous polypeptide.

89 . The composition of claim 78 , wherein the β2-microglobulin polypeptide comprises an amino acid sequence at least 90% identical to amino acids 21 to 113 of SEQ ID NO: 2.

90 . The composition of claim 89 , wherein the β2-microglobulin polypeptide comprises amino acids 21 to 113 of SEQ ID NO: 2.

91 . The composition of claim 89 , wherein the β2-microglobulin polypeptide comprises amino acids 1 to 119 of SEQ ID NO: 2.

92 . The composition of claim 82 , wherein the α-galactosylceramide comprises the formula:

wherein
R1 is a linear or branched C 2 -C 27 alkene with at least one C═C bond but not —(CH 2 ) 7 CH═CH(CH 2 ) 7 CH 3 , or R1 is C(OH)—R3 wherein R3 is a linear or branched C 2 -C 26 alkene with at least one C═C bond; and
R2 is one of the following (a)-(e):
(a) —CH 2 (CH 2 ) x CH 3 ,
(b) —CH(OH)(CH 2 ) x CH 3 ,
(c) —CH(OH)(CH 2 ) x (CH)(CH 3 ) 2 ,
(d) —CH═CH(CH 2 ) x CH 3 , and
(e) —CH(OH)(CH 2 ) x CH(CH 3 )CH 2 CH 3 ,

wherein X is an integer ranging from 5-17.

93 . The composition of claim 78 , wherein the composition further comprises a costimulatory molecule.

94 . The composition of claim 93 , wherein the costimulatory molecule is a Saponin, a toll-like receptor (“TLR”), B7-1 (CD80) or B7-2 (CD86).

Assignees

• Vaccinex Inc

Inventors

• Donda Alena
• Mach Jean-Pierre
• Stirnemann Kathrin
• Zauderer Maurice

Classifications

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title