The present disclosure provides immunomodulatory fusion proteins comprising a collagen-binding domain operably linked to an immunomodulatory domain. The disclosure also features compositions and methods of using the same, for example, to treat cancer.

It is disclosed herein that (a) an anti-tumor DNA vaccine delivered using a MIP DNA vector is a less effective tumor treatment than the corresponding anti-tumor DNA vaccine delivered using a conventional pDNA vector, despite the MIP DNA vector eliciting a higher frequency of antigen-specific CD8+ T cells; and (b) tumor infiltrating CD8+ T cells in animals immunized with the MIP DNA vector express higher levels of the immune checkpoint protein LAG-3 than animals immunized with a conventional pDNA vector, while the expression levels of other immune checkpoint proteins was the same for both groups. Based on these findings, improved methods and compositions for administering DNA vaccines are disclosed. Specifically, DNA vaccines delivered with MIP DNA are administered along with a LAG-3 pathway blocking agent, resulting in a more effective vaccine-induced cellular immune response.

The invention provides compositions and methods for treating diseases associated with expression of a cancer associated antigen as described herein. The invention also relates to chimeric antigen receptor (CAR) specific to a cancer associated antigen as described herein, vectors encoding the same, and recombinant T cells comprising the CARs of the present invention. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises an antigen binding domain that binds to a cancer associated antigen as described herein.

A vaccination method is provided. The method comprises administering to a mammal a histone deacytelase inhibitor in conjunction with a vaccine that expresses an antigen to which the mammal has a pre-existing immunity.

The present invention includes methods and compositions for treating cancer, whether a solid tumor or a hematologic malignancy. By expressing a chimeric antigen receptor in a monocyte, macrophage or dendritic cell, the modified cell is recruited to the tumor microenvironment where it acts as a potent immune effector by infiltrating the tumor and killing the target cells. One aspect includes a modified cell and pharmaceutical compositions comprising the modified cell for adoptive cell therapy and treating a disease or condition associated with immunosuppression.

The invention features methods to induce and maintain a protective cytotoxic T-lymphocyte response to a peptide of the HER2/neu oncogene, E75, with the effect of inducing and maintaining protective or therapeutic immunity against breast cancer in a patient in clinical remission. The methods comprise administering to the patient an effective amount of a vaccine composition comprising a pharmaceutically acceptable carrier, an adjuvant such as recombinant human GM-CSF, and the E75 peptide at an optimized dose and schedule. The methods further comprise administering an annual or semi-annual booster vaccine dose due to declining E75-specific T cell immunity. The invention also features vaccine compositions for use in the methods.

Disclosed are compositions of matters, cells, and treatment protocols useful for induction of anticancer responses in a patient suffering from cancer. In one embodiment the invention provides the use of NR2F6 silencing or gene editing in cord blood cells possessing anti-tumor activity in order to induce potentiated killer cells suitable for therapeutic use. In one embodiment said allogeneic cord blood killer cells are administered to initiate a cascade of antitumor immune responses, with initially responses mediated by allogeneic killer cells, and followed by endogenous immune responses.

Disclosed are compositions, methods, and kits for treating a cancer or pre-cancer. In particular, the invention generally relates to cancer vaccines as well as methods of delivering the vaccines. Combination treatments including the vaccines in combination with immunomodulatory agents are also contemplated.

The present invention relates to parvovirus mutated structural proteins comprising insertions of mimotopes of a HER2, compositions, multimeric structures, medicaments and vaccines comprising the same, nucleic acids, expression cassettes, constructs, vectors and cells comprising the nucleic acids, methods of preparing the structural proteins and methods of inducing a B-cell response or of treating a HER2-related disease.

The present invention provides humanized monoclonal antibodies, bi-specific antibodies, antibody conjugates, and fusion proteins that bind to the chemokine receptor CCR4. This antibody is derived from CCR4-IgG1 and recognizes the same epitope. This antibody contains either an IgG4 or a stabilized IgG4 in order to improve binding efficiency and reduce in vivo Fab arm exchange. Binding of the antibodies disclosed herein to CCR4 inhibits ligand-mediated activities and is used to treat symptoms of cancer.