Disclosed are potent immuno-DASH inhibitors and their use in the treatment of cell proliferative diseases.

Provided are methods for treating a disease using bioengineered enucleated cells. Also provided herein are compositions comprising enucleated cells, wherein the enucleated cells have been loaded with clinically relevant biomolecules.

We have developed novel shear-thinning biomaterials using silica nanoparticles, gelatin-based polymers and polypeptides such as anti-PD-1 antibodies. Shear-thinning biomaterial technology offers enables polymers and drugs loaded inside such polymers to be easily delivered directly through catheters into target area for use, for example, in cancer therapy and immunotherapy. When a force above a certain threshold is applied to inject such materials, they “thin” and behaves as a semi-solid, allowing the material to readily flow through a catheter. When the force is removed, the material instantly becomes a soft solid with significant cohesive properties that prevent it from dislodging or breaking up.

This document provides novel compositions and methods utilizing immunomodulating agents that can stimulate or indirectly augment the immune system, or can have an immunosuppressive effect. TNFR25 agonists disclosed herein have an anti-inflammatory and healing effect. They can be used, e.g., to treat disease caused by asthma and chronic inflammation, such as inflammatory bowel diseases including ulcerative colitis and Crohn's Disease. TNFR25 antagonists disclosed herein can inhibit CD8 T cell-mediated cellular immune responses and can, for example, mitigate organ or tissue rejection following a tissue transplantation. TNFR25 agonists disclosed herein represent biological response modifiers that alter the interaction between the body's cellular immune defenses and cancer cells to boost, direct, or restore the body's ability to fight the cancer when given with tumor vaccines. TNFR25 specific immunotoxins disclosed herein are also capable of increasing the effectiveness of a chemotherapeutic regimen by depleting a cancer patient of naturally occurring immunosuppressive cells.

This document provides novel compositions and methods utilizing immunomodulating agents that can stimulate or indirectly augment the immune system, or can have an immunosuppressive effect. TNFR25 agonists disclosed herein have an anti-inflammatory and healing effect. They can be used, e.g., to treat disease caused by asthma and chronic inflammation, such as inflammatory bowel diseases including ulcerative colitis and Crohn's Disease. TNFR25 antagonists disclosed herein can inhibit CD8 T cell-mediated cellular immune responses and can, for example, mitigate organ or tissue rejection following a tissue transplantation. TNFR25 agonists disclosed herein represent biological response modifiers that alter the interaction between the body's cellular immune defenses and cancer cells to boost, direct, or restore the body's ability to fight the cancer when given with tumor vaccines. TNFR25 specific immunotoxins disclosed herein are also capable of increasing the effectiveness of a chemotherapeutic regimen by depleting a cancer patient of naturally occurring immunosuppressive cells.

The present invention includes a method of preparing apoptotic bodies from a tumour and immunogenic compositions thereof. The method of preparation comprises: obtaining human tumour cells from a subject, inducing apoptosis of the human tumour cells with a drug or a physical treatment, and collecting apoptotic bodies from the apoptotic human tumour cells by centrifugation. The method comprises two centrifugation steps, low-speed at 50 g for 5 minutes to pellet cells, followed by high-speed centrifugation of the obtained supernatant at 3,000 g for 8 minutes to pellet apoptotic bodies. The purity of the apoptotic bodies (also referred to as immunogenic Tumor Apoptotic Bodies (TABi)) was determined by FACS to be 82.22%.

The present specification provides methods for augmenting the antigenic content, especially of tumor-associated antigens (TAA), and immunogenicity of cancer cells; methods for enhancing cross-presentation in dendritic cells, compositions comprising such manipulated cells derived from single cancer patients; and methods of using those compositions as a personal immunotherapeutic product to treat the donor patient's cancer.

The present specification provides methods for augmenting the antigenic content, especially of tumor-associated antigens (TAA), and immunogenicity of cancer cells; methods for enhancing cross-presentation in dendritic cells, compositions comprising such manipulated cells derived from single cancer patients; and methods of using those compositions as a personal immunotherapeutic product to treat the donor patient's cancer.

Provided herein is a method for making a tissue engineering scaffold. The method includes layering at least one sheet of cells onto a flexible scaffold, casting the sheets into geometries, and thereby creating the tissue engineering scaffold. Preferred geometry are non-linear (i.e. not a substantially flat surface such as may be provided by a flat glass substrate). The flexible scaffold is characterized by tensile strength, viscosity, stress, strain, modulus of polymers, or any combination thereof.

Compositions and methods for treating cancer in a subject in need thereof is provided. In certain embodiments, the method includes administering therapy-induced senescent (TIS) cells and an immune checkpoint inhibitor to the subject. Also provided are compositions comprising therapy-induced senescent (TIS) cells.