Combination therapy with semaphorin-4D blockade (SEMA4D) and DC1 therapy
Disclosed are compositions and methods comprising the administration of pulsed dendritic cells and an immunoregulator molecule inhibitor for the treatment of cancer.
1. An anti-cancer combination therapy comprising at least one dendritic cell pulsed with a human epidermal growth factor receptor 2 (HER2) oncodriver formulated for intratumoral administration and at least one immunoregulatory molecule inhibitor comprising an antibody or an antigen-binding fragment thereof that binds specifically to Semaphorin 4D (SEMA4D) formulated for systemic administration; and wherein administration of the combination therapy results in tumor shrinkage of injected and non-injected tumors.
2. The anti-cancer combination therapy of claim 1 , wherein the oncodriver pulsed dendritic cell is activated with interleukin-12 (IL-12) prior to administration.
3. The anti-cancer combination therapy of claim 1 or claim 2 , wherein the antagonist antibody that specifically binds to SEMA4D comprises pepinemab.
4. The anti-cancer combination therapy of claim 1 , wherein the anti-SEMA4D antibody or antigen-binding fragment thereof blocks SEMA4D binding to its receptor.
5. The anti-cancer combination therapy of claim 1 , wherein the anti-SEMA4D antibody or antigen-binding fragment thereof comprises a variable heavy chain (VH) comprising VHCDRs 1-3comprising SEQ ID NOs 5, 6, and 7, respectively and a variable light chain comprising VLCDRs 1-3 comprising SEQ ID NOs 8, 9, and 10, respectively.
6. The anti-cancer combination therapy of claim 1 , wherein the anti-SEMA4D antibody or antigen-binding fragment thereof comprises a VH and a VL comprising the amino acid sequences SEQ ID NO: 3 and SEQ ID NO: 4, respectively.