Provided are antibodies that specifically bind Vaccinia Virus (VV) A56 or B5 antigen. Also provided are fusion proteins and conjugates that comprise the antibodies. Pharmaceutical compositions and kits that comprise the antibodies, fusion proteins and conjugates are also provided. Aspects of the present disclosure further include methods of using the antibodies, fusion proteins and conjugates, e.g., for therapeutic purposes. In certain embodiments, provided are methods that comprise administering an antibody, fusion protein or conjugate of the present disclosure to an individual having cancer, wherein the individual comprises cancer cells infected with VV, and wherein the antibody, fusion protein or conjugate is targeted to the infected cancer cells by VV antigens expressed on the surface of the infected cancer cells. Aspects of the present disclosure further include methods of targeting an antibody, fusion protein, or conjugate that specifically binds an oncolytic virus (OV) antigen to cancer cells in an individual.

As described below, the present invention features genetically modified immune cells having enhanced anti-neoplasia activity, resistance to immune suppression, and decreased risk of eliciting a graft versus host reaction, or a combination thereof. The present invention also features methods for producing and using these modified immune effector cells.

Certain aspects of the present invention are directed to a method for making a protein blocking assembly reversibly linking a therapeutic protein to a blocking group via a linker moiety. Additional aspects of the invention are directed to the protein blocking assembly, and to methods of administering the protein blocking assembly to a subject, where the protein is cleaved from the protein blocking assembly.

Provided for herein in several embodiments are immune cell-based compositions comprising BCMA-directed chimeric antigen receptors (CAR). In several embodiments, the immune-cell based compositions also target an additional tumor marker and/or an additional epitope of BCMA. In several embodiments, the BCMA-directed CAR is expressed in a Natural Killer cell. In several embodiments, combinations of BCMA-CAR-expressing NK cells are administered in conjunction with, for example CAR-expressing NK cells and/or CAR-expressing T cells that are directed to an additional cancer marker and/or an additional epitope of BCMA. Also provided for herein are methods and uses of the chimeric antigen receptors in immunotherapy.

Disclosed are a natural killer (NK) cell expressing an anti-cotinine chimeric antigen receptor (CAR) specifically binding to cotinine, and a cell therapeutic agent containing the NK cell. The CAR-expressing NK cell which specifically binds cotinine, can effectively move to tumor tissue, regardless of the kind of cancer, depending on the binding substance bound to cotinine. Therefore, the natural killer cell can be usefully employed as a gene therapy exhibiting a highly efficient anticancer effect.

The present disclosure presents a general approach to engineering existing protein-protein interactions through domain addition and evolution. The disclosure teaches the creation of novel fusion proteins that include knottin peptides where a portion of the knottin peptide is replaced with a sequence that has been created for binding to a particular target. Such fusion proteins can also be bispecific or multi specific in that they can bind to and/or inhibit two or more receptors or receptor ligands. Knottins may be fused with an existing ligand (or receptor) as a general platform tor increasing the affinity of a ligand-receptor interaction or for creating a multi specific protein. In addition, the fusion proteins may comprise a knottin peptide fused to another protein where the other protein facilitates proper expression and folding of the knottin.

The present disclosure presents a general approach to engineering existing protein-protein interactions through domain addition and evolution. The disclosure teaches the creation of novel fusion proteins that include knottin peptides where a portion of the knottin peptide is replaced with a sequence that has been created for binding to a particular target. Such fusion proteins can also be bispecific or multi specific in that they can bind to and/or inhibit two or more receptors or receptor ligands. Knottins may be fused with an existing ligand (or receptor) as a general platform tor increasing the affinity of a ligand-receptor interaction or for creating a multi specific protein. In addition, the fusion proteins may comprise a knottin peptide fused to another protein where the other protein facilitates proper expression and folding of the knottin.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

The present invention relates to a peptide compound of PDL2 selected from a peptide fragment, a functional homologue, and a functional analogue, as well as to a nucleic acid, such as DNA or RNA, encoding the peptide compound, a vector, such as a virus vector, and a host cell, such as mammalian cell, comprising the vector. The peptide compound, nucleic acid, vector and host cell of the present invention are in particular, useful for the treatment or prevention of a cancer characterized by expression of PDL2.