The present invention relates to a polypeptide binding to mucin 1, an isolated polynucleotide encoding same, a vector carrying the polynucleotide, and a cell including the vector. In addition, the present invention relates to a chimeric antigen receptor including the polypeptide binding to mucin 1, an isolated polynucleotide encoding the chimeric antigen receptor, a vector carrying the polynucleotide, an immune cell expressing the chimeric antigen receptor, a composition comprising same for treatment of cancer, and a method for treatment of cancer.

Described herein are engineered cytokine receptor switches that can include a signal peptide, an extracellular activator binding domain, a hinge, a transmembrane domain, and/or an intracellular signaling domain. Binding of an activator to the activator binding domain can activate cytokine signaling through the intracellular signaling domain. These cytokine receptor switches can be expressed in immune cells, sometimes in combination with a chimeric antigen receptor (CAR), to increase immune cell persistence by promoting adoption of memory-like phenotypes. Also described herein are methods of using engineered cytokine receptors in immune cell therapies, such as CAR T-cell therapy, to improve patient outcomes and prevent disease relapse.

An antibody or an antigen-binding fragment thereof is capable of specifically binding to MUC17. The antibody or the antigen-binding fragment thereof can specifically bind to MUC17 with high affinity and can be used as a drug for treating malignant gastrointestinal tumors.

The present invention relates to compositions and methods that provide novel therapies in cancer. The invention includes a phagocytic cell modified with a repressor of signal regulatory protein-alpha (SIRP) and bound to a targeting antibody to enhance phagocytic activity of the phagocytic cell toward tumor tissue. Methods of enhancing phagocytic activity and treating a tumor are also included.

In certain embodiments, this disclosure provides methods to generate DNA, RNA and/or DNA-peptide nanostructures based chimeric antigen receptor (CAR) T cell (engineered T cell) for cancer immunotherapy, and compositions made by these methods.

A fusion protein comprising: a first component comprising an antibody, or a fragment or variant thereof; and a second component comprising a cytokine trap or an adenosine deaminase or a fragment or variant thereof. In certain embodiments, the antibody is an anti-PD-1 antibody. In certain embodiments, the antibody binds to a tumor antigen, for example a MUC16 or MUC1 antigen. In certain embodiments, the cytokine trap is a TGF- trap. A polynucleotide encoding such a fusion protein and a vector comprising such a polynucleotide. A composition comprising the fusion protein. A method of using the composition, including in the treatment of cancer.

MUC1 is overexpressed in many cancers, including those of the lung, colon, breast, ovary, and pancreas. Aspects of the invention are directed towards the discovery of monoclonal antibodies and fragments thereof, such as a human single chain variable fragment (scFv), that recognizes human MUC1-SEA.

Antibodies specific to MUC18 (a.k.a. MCAM or CD146) and antibody-drug conjugates (ADCs) comprising such. Also provided herein are uses the the anti-MUC18 antibodies or ADCs for therapeutic and diagnostic purposes.

A ribonucleic acid comprising two non-natural pre-miRNA sequences, wherein each pre-miRNA sequence comprises a guide miRNA that inhibits the expression of an immune checkpoint protein. The pre-miRNA sequences may target a different gene or target a different regions of the same gene. A deoxyribonucleic acid encoding the aforementioned ribonucleic acid. The deoxyribonucleic acid may further encode a protein such as a chimeric antigen receptor, a cytokine, a cell tag, and/or an immune checkpoint inhibitor. A vector comprising the aforementioned ribonucleoic acid or the aforementioned deoxyribonucleic acid. A method for modifying the expression of a gene in a cell, wherein the method comprises introducing the aforementioned ribonucleic acid or the aforementioned deoxyribonucleic acid to the cell. A method for producing a genetically-engineered cell, wherein the method comprises introducing the aforementioned ribonucleic acid or the aforementioned deoxyribonucleic acid to the cell. A genetically-modified cell comprising the aforementioned ribonucleic acid or the aforementioned deoxyribonucleic acid. A composition comprising the aforementioned ribonucleic acid or the aforementioned deoxynbonucleic acid. A kit comprising the aforementioned ribonucleic acid or the aforementioned deoxyribonucleic acid. A method of treating a disease or disorder in a subject, comprising administering the aforementioned ribonucleic acid or the aforementioned deoxyribonucleic acid to the subject. A method of treating a disease or disorder in a subject, comprising administering the aforementioned cell to the subject. The use of the aforementioned ribonucleic acid or the aforementioned deoxyribonucleic acid in the manufacture of a medicament for modifying the expression of a gene. The use of the aforementioned ribonucleic acid or the aforementioned deoxyribonucleic acid in the manufacture of a medicament for the treatment of a disease or disorder in a subject.

In alternative embodiments, provided are compositions, including products of manufacture and kits, and methods, for engineering immune effector cells, e.g., T cells, NK cells, monocytes and/or macrophages to recognize and destroy a desired target cell, which can be a cancer cell, a dysfunctional cell, or an infected cell.