Fusion proteins comprising an anti-CD40 antibody and cancer antigens
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.
1. 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, 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, and wherein the one or more cancer antigens comprise a cyclin D1 antigen, cyclin B1 antigen, HPV E6 and/or E7 antigen, PSA, survivin antigen, or melanoma antigen.
2. The composition of claim 1 , wherein the antigen is fused to the carboxy terminus of the light chain or heavy chain of the antibody.
3. The composition of claim 2 , wherein one or more cancer antigens are fused to the carboxy terminus of the heavy chain of the anti-CD40 antibody.
4. The composition of claim 1 , wherein the one or more cancer antigens are tumor associated antigens selected from CEA, HER-2/neu, BAGE, GAGE, MAGE 1-4, 6 and 12, MUC-1, MUC-2, GM2 ganglioside, GD2 ganglioside, ras, myc, tyrosinase, MART, MARCO-MART, Pmel 17, GnT-V intron V sequence, Prostate Ca psm, PRAME, β-catenin, MUM-1-B (melanoma ubiquitous mutated gene product), BAGE (melanoma antigen) 2-10, EBNA (Epstein-Barr Virus nuclear antigen) 1-6, gp75, p53, lung resistance protein (LRP), Bcl-2, and Ki-67.
5. The composition of claim 1 , wherein the one or more cancer antigens comprise one or more HPV antigens.
6. The composition of claim 5 , wherein the one or more cancer antigens comprise an E6 and/or E7 HPV antigen.
7. The composition of claim 6 , wherein the one or more cancer antigens comprise an E6 and E7 antigen.