The present invention relates to Chimeric Antigen Receptors (CAR) that are recombinant chimeric proteins able to redirect immune cell specificity and reactivity toward selected membrane antigens, and more particularly in which extracellular ligand binding is a scFV derived from a BCMA monoclonal antibody, conferring specific immunity against BCMA positive cells. The engineered immune cells endowed with such CARs are particularly suited for treating lymphomas, multiple myeloma and leukemia.

The present disclosure provides a heterodimeric, conditionally active chimeric antigen receptor (CAR), and a nucleic acid comprising a nucleotide sequence encoding the CAR. The present disclosure provides cells genetically modified to produce the CAR. A CAR of the present disclosure can be used in various methods, which are also provided.

The present invention provides a bi-specific molecule which comprises: (i) a first domain which binds B cell maturation antigen (BCMA) and comprises at least part of a proliferation-inducing ligand (APRIL); and (ii) a second domain capable of activating a T cell. The invention also provides the use of such a molecule in the treatment of plasma-cell mediated diseases, such as multiple myeloma.

Provided herein are improved gene therapy vectors and methods of use, in some embodiments, comprising sequences for improved expression and cellular targeting of a therapeutic protein.

Provided herein are multi-domain immunomodulatory proteins, nucleic acids encoding such immunomodulatory proteins, cells engineered to express the immunomodulatory proteins and infectious agents containing nucleic acid encoding the immunomodulatory proteins. The immunomodulatory proteins bind both an inhibitory receptor and a receptor involved in activation signaling cascades in an immune cell, such as a T cell. The immunomodulatory proteins, engineered cells and infectious agents provide therapeutic utility for a variety of immunological diseases or conditions. Compositions and methods for making and using such proteins are provided.

Provided herein, in some embodiments, are AFFIMER® polypeptides that binds to the neonatal Fc receptor (FcRn) and extends the half-life of the polypeptides. Also provided herein, in some embodiments, are compositions containing the polypeptides, methods of using the polypeptides, and methods of producing the polypeptides.

The invention provides chimeric antigen receptor(s) (CAR(s)) that comprise a fusion protein of CTX or any functional variant thereof or a CTX-like peptide or any functional variant thereof as the extracellular antigen recognition moiety of the CAR. CAR(s) comprising CTX, a CTX-like peptide or functional variants of the foregoing are collectively referred to herein as “CTX-CAR(s).” Such CTX-CAR(s) may further comprise additional moieties or domains in the extracellular domain, a transmembrane domain and at least one intracellular signaling domain. Such CTX-CAR(s) may be expressed in a host cell, such as, but not limited to, an immune effector cell. The present invention also provides methods of treatment (such as, for example, methods for treating cancer) by providing to the patient in need thereof immune effector cells that arc engineered to express a CTX-CAR described herein.

Implantable scaffolds that treat solid tumors and escape variants and that provide effective vaccinations against cancer recurrence are described. The scaffolds include genetically-reprogrammed lymphocytes and a lymphocyte-activating moiety.

The present invention relates to a fusion protein in which a target protein and an Oct-1 protein-containing protein tag are linked, an expression structure comprising a nucleotide sequence encoding same, a recombinant vector including same, and a transformed cell including same.

The present invention relates to pseudotyped retrovirus-like particles or retroviral vectors comprising both engineered envelope glycoproteins derived from a virus of the Paramyxoviridae family fused to a cell targeting domain and fused to a functional domain. The present invention also relates to the use of said pseudotyped retrovirus-like particles or retroviral vectors to selectively modulate the activity of specific subsets of cells, in particular of specific immune cells. These pseudotyped retrovirus-like particles or retroviral vectors are particularly useful for gene therapy, immune therapy and/or vaccination.