Methods and compositions to enhance the immunogenicity of tumors

A method of inhibiting tumor growth in a subject, wherein the tumor comprises tumor cells that express complement components, such as C3 and C5;

• complement receptors such as C3aR1, C5aR1, C5aR2, C1R, C1RL, CR2 and LAIR1;
• complement factors such as CFB, CFD, CFH, CFHR1, CFHR2, CFHR3, CFHR4, CFHR5, CFI and CFP;
• complement regulators such as C1QBP, CD46, CD55 and CD59;
• or cathepsins such as CTSB, CTSC, CTSD, CSTL, CSTO, or CTSS or any combination thereof, or any combination of said proteins or receptors thereof, the method comprising:
• a) administering to the subject a therapeutically effective amount of a first agent wherein the first agent decreases the expression of complement components, such as C3 and C5;
• complement receptors such as C3aR1, C5aR1, C5aR2, C1R, C1RL, CR2 and LAIR1;
• complement factors such as CFB, CFD, CFH, CFHR1, CFHR2, CFHR4, CFHR5, CFI and CFP;
• complement regulators such as C1QBP, CD46, CD55 and CD59;
• or cathepsins such as CTSB, CTSC, CTSD, CSTL, CSTO, or CTSS, or any combination thereof, in the tumor cells, and
• b) administering to the subject a therapeutically effective amount of a second agent wherein the second agent increases the expression, activity or production of complement protein C3d or a biologically active variant thereof including peptides derived from C3d, or other immunostimulatory peptides, in the tumor cells or the tumor micro-environment, thereby inhibiting the tumor growth in the subject.

A method of treating cancer, or preventing metastasis of cancer, in a subject, wherein the cancer cells express complement components, such as C3 and C5;

• complement receptors such as C3aR1, C5aR1, C5aR2, C1R, C1RL, CR2 and LAIR1;
• complement factors such as CFB, CFD, CFH, CFHR1, CFHR2, CFHR4, CFHR5, CFI and CFP;
• complement regulators such as C1QBP, CD46, CD55 and CD59;
• or cathepsins such as CTSB, CTSC, CTSD, CSTL, CSTO, or CTSS or any combination thereof, the method comprising:
• a) administering to the subject a therapeutically effective amount of a first agent wherein the first agent decreases the expression, activity or production of complement components, such as C3 and C5;
• complement receptors such as C3aR1, C5aR1, C5aR2, C1R, C1RL, CR2 and LAIR1;
• complement factors such as CFB, CFD, CFH, CFHR1, CFHR2, CFHR3, CFHR4, CFHR5, CFI and CFP;
• complement regulators such as C1QBP, CD46, CD55 and CD59;
• or cathepsins such as CTSB, CTSC, CTSD, CSTL, CSTO, or CTSS or any combination thereof, in the cancer cells, and
• b) administering to the subject a therapeutically effective amount of a second agent wherein the second agent increases the expression of complement protein C3d or peptides derived from within C3d or other immunostimulatory peptides in the cancer cells or tumor micro-environment, thereby treating cancer, or preventing metastasis of cancer, in the subject.

The method of claim 39, wherein the cancer treatment is administration of a treatment selected from the group consisting of:

• a checkpoint inhibitor;
• a proteasome inhibitor;
• immunotherapy;
• radiation therapy;
• chemotherapy.

A pharmaceutical composition comprising a therapeutically effective amount of a first agent that decreases the expression, production or activity of complement components, such as C3 and C5;

• complement receptors such as C3aR1, C5aR1, C5aR2, C1R, C1RL, CR2 and LAIR1;
• complement factors such as CFB, CFD, CFH, CFHR1, CFHR2 CFHR3, CFHR4, CFHR5, CFI and CFP;
• complement regulators such as C1QBP, CD46, CD55 and CD59;
• or cathepsins such as CTSB, CTSC, CTSD, CSTL, CSTO, or CTSS or any combination thereof, in a tumor cell, and a therapeutically effective amount of a second agent that increases the expression or activity of complement protein C3d or a biologically active variant thereof including peptides derived from C3d or other immunostimulatory peptides in the tumor cell or the tumor cell microenvirontnent, in a pharmaceutically acceptable medium.