Fusion proteins comprising an anti-cd40 antibody and cancer antigens

Patent metadata

Field	Value
Publication number	US-2021308242-A1
Application number	US-202117301704-A
Country	US
Kind code	A1
Filing date	Apr 12, 2021
Priority date	Mar 10, 2009
Publication date	Oct 7, 2021
Grant date	—

Abstract

The present invention includes compositions and methods for the expression, secretion and use of novel compositions for use as, e.g., vaccines and antigen delivery vectors, to delivery antigens to antigen presenting cells. In one embodiment, the vector is an anti-CD40 antibody, or fragments thereof, and one or more antigenic peptides linked to the anti-CD40 antibody or fragments thereof, including humanized antibodies.

First claim

1 .- 58 . (canceled)

59 . A method for inducing cytotoxic T-cell response against tumor cells in a subject in need thereof, the method comprising administering to the subject an effective amount of a composition comprising a fusion protein, wherein the fusion protein comprises an anti-CD40 antibody or portion thereof linked to one or more cancer antigens.

60 . The method of claim 59 , wherein the cancer antigens are selected from tumor associated antigens selected from CEA, prostate specific antigen (PSA), HER-2/neu, BAGE, GAGE, MAGE 1-4, 6 and 12, MUC (Mucin) (e.g., MUC-1, MUC-2, etc.), GM2 and GD2 gangliosides, ras, myc, tyrosinase, MART (melanoma antigen), MARCO-MART, cyclin B1, cyclin D1, Pmel 17(gp100), GnT-V intron V sequence (N-acetylglucoaminyltransferase V intron V sequence), Prostate Ca psm, prostate serum antigen (PSA), PRAME (melanoma antigen), β-catenin, MUM-1-B (melanoma ubiquitous mutated gene product), GAGE (melanoma antigen) 1, BAGE (melanoma antigen) 2-10, c-ERB2 (Her2/neu), EBNA (Epstein-Barr Virus nuclear antigen) 1-6, gp75, human papilloma virus (HPV) E6 and E7, p53, lung resistance protein (LRP), Bcl-2, survivin, and Ki-67.

61 . The method of claim 60 , wherein the tumor antigen comprises a cyclin D1 antigen, cyclin B1 antigen, HPV E6 and E7 antigen, PSA, survivin antigen, or melanoma antigen.

62 . The method of claim 61 , wherein the one or more cancer antigens comprise one or more HPV antigens.

63 . The method of claim 62 , wherein the one or more cancer antigens comprise an E6 and E7 HPV antigen.

64 . The method of claim 63 , wherein one or more cancer antigens are fused to the carboxy terminus of the heavy chain of the anti-CD40 antibody.

65 . The method of claim 59 , wherein the subject has and/or has been diagnosed with leukemia, multiple myeloma, prostate cancer, cervical cancer, ovarian, cancer, vaginal cancer, melanoma, mantle cell lymphoma, or breast cancer.

66 . The method of claim 59 , wherein the antigen is fused to the carboxy terminus of the light chain or heavy chain of the antibody.

67 . The method of claim 59 , wherein the anti-CD40 antibody comprises the anti-CD40 12E12.3F3 antibody or a humanized version thereof.

68 . The method of claim 59 , wherein the anti-CD40 antibody or portion thereof comprises a light chain variable region comprising a CDR1L, CDR2L, and CDR3L of SEQ ID NO:41, 42, and 43, respectively, and a heavy chain variable region comprising a CDR1H, CDR2H, and CDR3H of SEQ ID NO:44, 45, and 46, respectively.

69 . A method for treating cancer in a subject, the method comprising administering to the subject an effective amount of a composition comprising a fusion protein, wherein the fusion protein comprises an anti-CD40 antibody or portion thereof linked to one or more cancer antigens.

70 . The method of claim 69 , wherein the cancer antigens are selected from tumor associated antigens selected from CEA, prostate specific antigen (PSA), HER-2/neu, BAGE, GAGE, MAGE 1-4, 6 and 12, MUC (Mucin) (e.g., MUC-1, MUC-2, etc.), GM2 and GD2 gangliosides, ras, myc, tyrosinase, MART (melanoma antigen), MARCO-MART, cyclin B1, cyclin D1, Pmel 17(gp100), GnT-V intron V sequence (N-acetylglucoaminyltransferase V intron V sequence), Prostate Ca psm, prostate serum antigen (PSA), PRAME (melanoma antigen), β-catenin, MUM-1-B (melanoma ubiquitous mutated gene product), GAGE (melanoma antigen) 1, BAGE (melanoma antigen) 2-10, c-ERB2 (Her2/neu), EBNA (Epstein-Barr Virus nuclear antigen) 1-6, gp75, human papilloma virus (HPV) E6 and E7, p53, lung resistance protein (LRP), Bcl-2, survivin, and Ki-67.

71 . The method of claim 69 , wherein the tumor antigen comprises a cyclin D1 antigen, cyclin B1 antigen, HPV E6 and E7 antigen, PSA, survivin antigen, or melanoma antigen.

72 . The method of claim 71 , wherein the one or more cancer antigens comprise one or more HPV antigens.

73 . The method of claim 72 , wherein the one or more cancer antigens comprise an E6 and E7 HPV antigen.

74 . The method of claim 73 , wherein one or more cancer antigens are fused to the carboxy terminus of the heavy chain of the anti-CD40 antibody.

75 . The method of claim 69 , wherein the subject has and/or has been diagnosed with leukemia, multiple myeloma, prostate cancer, cervical cancer, ovarian, cancer, vaginal cancer, melanoma, mantle cell lymphoma, or breast cancer.

76 . The method of claim 69 , wherein the antigen is fused to the carboxy terminus of the light chain or heavy chain of the antibody.

77 . The method of claim 69 , wherein the anti-CD40 antibody comprises the anti-CD40 12E12.3F3 antibody or a humanized version thereof.

78 . The method of claim 69 , wherein the anti-CD40 antibody or portion thereof comprises a light chain variable region comprising a CDR1L, CDR2L, and CDR3L of SEQ ID NO:41, 42, and 43, respectively, and a heavy chain variable region comprising a CDR1H, CDR2H, and CDR3H of SEQ ID NO:44, 45, and 46, respectively.

Assignees

• Baylor Res Institute

Inventors

• Zurawski Gerard
• Banchereau Jacques F
• Flamar Anne-Laure
• Klucar Peter
• Akagawa Keiko
• Zurawski Sandra
• Oh Sangkon

Classifications

• C07K16/2878 Primary

  against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 · CPC title

• A61K39/00

  Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53) · CPC title

• A61K39/001129 Primary

  Molecules with a "CD" designation not provided for elsewhere · CPC title

• C07K2317/80

  remaining in the (producing) cell, i.e. intracellular antibodies or intrabodies · CPC title

• C12N2770/24234

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title