Methods and compositions for modifying allogeneic donor T cells for use in the treatment of high risk leukemias are provided.

The present invention relates to a method for producing natural killer cells using T cells, and more particularly, to a method for producing natural killer cells, which comprises culturing seed cells using CD4 (+) T cells as feeder cells. The method for producing natural killer cells using T cells according to the present invention is a method capable of producing natural killer cells by selectively proliferating only natural killer cells from a small amount of seed cells while maintaining the high killing activity of the natural killer cells. The method of the present invention can produce a large amount of natural killer cells that can be frozen, and thus is useful for commercialization of cell therapeutic agents.

The invention relates to methods for treatment of cancers utilizing a combination of a deoxyribonuclease enzyme and adoptive cell immunotherapy comprising cells expressing a chimeric antigen receptor (CAR) or a T cell receptor (TCR). In particular embodiments, the deoxyribonuclease enzyme can be given parenterally or encoded by a vector or secreted by a cell comprising TCR or CAR.

Provided herein are polynucleotides encoding chimeric antigen receptors (CARs) comprising a CD19 antigen binding domain that specifically binds to CD19 and is resistant to rituximab binding; and immune cells comprising these CD19-specific CARs, e.g., CAR-T cells. Also provided are methods of making and using these CD19-specific CARs, and immune cells comprising these CD19-specific CARs.

The present disclosure relates to compounds (e.g., antibodies, antigen-binding fragments thereof, bispecific molecules, or chimeric antigen receptor polypeptides) that bind to a neoepitope of mutant nucleophosmin (NPM1c) in complex with, or presented by, a class I major histocompatibility complex (MHC class I) protein, or cells expressing such compounds, and their use in methods for treating, or ameliorating one or more symptoms of, cancer.

Disclosed herein are anti-mesothelin antibodies and antigen-binding fragments, chimeric antigen receptors (CARs) having these anti-mesothelin antibodies and antigen-binding fragments (mesothelin CARs) and genetically modified immune effector cells having such mesothelin CARs. Polynucleotides encoding the anti-mesothelin antibodies and antigen-binding fragments and mesothelin CARs are also provided herein. Compositions comprising anti-mesothelin antibodies and antigen-binding fragments and mesothelin CARs are also provided herein. The present disclosure also relates to uses of the anti-mesothelin antibodies and antigen-binding fragments and genetically modified immune effector cells having such mesothelin CARs in cancer treatment.

Hematopoietic stem/progenitor cells (HSPC) and/or non-T effector cells are genetically modified to express (i) an extracellular component including a ligand binding domain that binds a cellular marker preferentially expressed on an unwanted cell; and (ii) an intracellular component comprising an effector domain. Among other uses, the modified cells can be administered to patients to target unwanted cancer cells without the need for immunological matching before administration.

Novel therapeutic immunotherapy compositions comprising at least two vectors, each vector encoding a functional CAR, whereby the combination of vectors results in the expression of two or more non-identical binding domains, wherein each vector encoded binding domain(s) are covalently linked to a transmembrane domain and one or more non-identical intracellular signaling motifs are provided herein as well as are methods of use of same in a patient-specific immunotherapy that can be used to treat cancers and other diseases and conditions.

The present disclosure provides modified immune cell (e.g., modified T cell) comprising an exogenous T cell receptor (TCR) having specificity for NY-ESO-1. The present disclosure provides modified immune cells or precursors thereof (e.g., modified T cells) comprising an exogenous TCR and a switch receptor. Gene edited modified cells are also provided, such that the expression of one or more of an endogenous T-cell receptor gene (e.g., TRAC, TRBC) or an endogenous immune checkpoint gene (e.g. PD-1 or TIM-3) is downregulated.

The present invention provides methods and compositions related to multivalent carbohydrate antigen structures comprising cancer or infection associated ganglioside carbohydrate antigens. Said carbohydrate structures may be used to induce immunity against said carbohydrate antigens. In some embodiments, carbohydrate structures may be administered to a subject thereby inducing immunity in the subject, for example, the administration of a vaccine comprising said carbohydrate structure. Also provided are methods to induce an immune response in a subject in need thereof by administering said carbohydrate structure. Further provided are methods of producing an antibody or TCR that bind said carbohydrate antigens.