The present invention relates to novel antigen binding proteins for binding to dysfunctional P2X.sub.7 receptor.

Provided are methods for disrupting Pdcd1, Adora2a, and Ctla4 genes using a Cas and guide RNAs targeting the three genes. Also provided are methods for treatment of cancers and/tumors by administering to subjects in need thereof engineered immune cells wherein the Pdcd1, Adora2a, and Ctla4 genes are disrupted in the engineered immune cells and wherein the engineered immune cells optionally further comprise a chimeric antigen receptor for targeting cancer or tumor cells.

The present invention relates to compositions and methods or uses of those compositions for amplifying immune activity to treat a variety of diseases or conditions, particularly cancer. A method for treating a condition comprising administering to a subject an antigen binding protein comprising (i) a first antigen binding domain that binds to a tumour-specific antigen; and (ii) a second antigen binding domain that binds to a cell surface molecule on an immune cell, thereby treating the condition. Preferably, further comprising a bridging molecule comprising (i) a targeting moiety that binds to a cell surface molecule on a target cell; and (ii) a tumour-specific antigen epitope moiety that is bound by the first antigen binding domain of the antigen binding protein.

This invention provides an isolated or purified T-cell receptor (TCR) having antigenic specificity for the mutated human p53R175H. The inventive TCR can recognize the HLA-A2 restricted mutant p53R175H peptide (HMTEVVRHC) but cannot recognize the wild-type p53R175 peptide (HMTEVVRRC). The inventive TCR can also be activated by tumor cells harboring a mutated human p53R175H in the context of HLA-A2. The invention further provides related polypeptides, proteins, nucleic acids, recombinant expression vectors, host cells, populations of cells and pharmaceutical compositions relating to the TCR of the invention. Methods of treating or preventing cancer in a mammal are further provided by the invention.

The present invention provides a method of creating a chemically-induced heterodimerizing system having three different components that form a ternary complex by amendment of a chemically induced homodimerizing system, wherein said chemically induced homodimerizing system comprises two components for the homodimerization, wherein the antigen binding domain comprising SEQ ID NO:1 (AB0) is the first component and a small molecule such as caffeine is the second component of the homodimerization, and wherein said AB0 and said small molecule form a complex of AB0/AB0/small molecule. Heterodimerizing systems obtained by said method are also disclosed herein.

Provided are genetically engineered induced pluripotent stem cells (iPSCs) and derivative cells thereof expressing mono- and/or bi-specific chimeric antigen receptors (CAR) with anti-CD133 and anti-EGFR antigen binding domains, and methods of using the same. Also provided are compositions, polypeptides, vectors, and methods of manufacturing.

There is provided method for making a cell composition which comprises step of transducing a population of cells with a mixture of at least two viral vectors, wherein at least one vector comprises a nucleic acid sequence which encodes a chimeric antigen receptor (CAR); and wherein at least one vector comprises a nucleic acid encoding an activity modulator which modulates the activity of the CAR, of a cell expressing the CAR, or of a target cell. There is also provided a cell composition made by such a method and its use in the treatment of diseases such as cancer.

Dual-chimeric antigen receptor (CAR) cell systems are disclosed that can be used with adoptive cell transfer to target and kill cancers expressing tumor antigens (TA) that are also expressed on healthy hematopoietic cells. In some embodiments, the dual CAR cell expresses a first CAR polypeptide that contains in an ectodomain a binding agent that can selectively bind CD83 on CD83-expressing cancer cells (anti-CD83 binding agent), and a second CAR polypeptide that contains in an ectodomain an antigen-binding agent that can bind a second tumor antigen that is expressed on both the cancer and healthy hematopoietic cells (anti-TA binding agent), such as CD33, CLEC12A, CD123, or FLT3.

The present disclosure provides adoptive T cell therapies that have improved architectures for targeting antigens and recruiting multimeric immune signaling complexes for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith.

An isolated immune cell, a method for preparing such modified immune cell, a method of treating a living being suffering or at risk of suffering from cancer or non-malignant diseases, an oligonucleotide and a use thereof.