Disclosed are protein switches that can sequester bioactive peptides and/or binding domains, holding them in an inactive (“off”) state, until combined with a second designed polypeptide called the key, which induces a conformational change that activates (“on”) the bioactive peptide or binding domain only when the protein switch components are co/localized when bound to their targets, components of such protein switches, and their use.

D domain (DD) containing polypeptides (DDpp) that specifically bind targets of interest (e.g., BCMA, CD123, CS1, HER2, AFP, and AFP p26) are provided, as are nucleic acids encoding the DDpp, vectors containing the nucleic acids and host cells containing the nucleic acids and vectors. DDpp such as DDpp fusion proteins, are also provided as are methods of making and using the DDpp. Such uses include, but are not limited to diagnostic and therapeutic applications.

Provided herein are compositions comprising recombinant mammalian cells that express recombinant T cell receptors with specificity against gp100 peptide:MHC antigens. Also provided are therapeutic methods of using the recombinant mammalian cells as cell therapies against melanoma tumors.

Described herein are protein scaffolds comprising an apelin (APJ) receptor binding domain. Described herein are the uses for the protein scaffolds in treating diseases or disorders comprising aberrant APJ receptor signaling.

Disclosed are compositions and methods for targeted treatment of glioblastoma multiforme (GBM). In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to target and kill Glioblastoma Stem Cells (GSCs). Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with Glioblastoma Stem Cells (GSCs) that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

The invention provides an isolated or purified T cell receptor (TCR) having antigenic specificity for a) melanoma antigen family A (MAGE A)-3 in the context of HLA-A1 or b) MAGE-A12 in the context of HLA-Cw7. The invention further provides related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, and populations of cells. Further provided by the invention are antibodies, or an antigen binding portion thereof, and pharmaceutical compositions relating to the TCRs of the invention. Methods of detecting the presence of cancer in a host and methods of treating or preventing cancer in a host are further provided by the invention.

Fibronectin type III (.sup.10Fn3) binding domains having novel designs that are associated with reduced immunogenicity are provided. The application describes alternative .sup.10Fn3 binding domains in which certain immunogenic regions are not modified when producing a binder in order to maintain recognition as a self antigen by the host organism. The application also describes .sup.10Fn3 binding domains in which HLA anchor regions have been destroyed thereby reducing the immunogenic contribution of the adjoining region. Also provided are .sup.10Fn3 domains having novel combinations of modified regions that can bind to a desired target with high affinity.

The present invention provides Tenascin-3 FnIII domain-based scaffolds that specifically bind to CD40L. The invention further provides engineered variants with increased affinity for the target. The present invention is also related to engineered scaffolds as prophylactic, diagnostic, or therapeutic agents, in particular for therapeutic uses against SLE and other autoimmune diseases and conditions.

Provided herein are recombinant masking proteins and recombinant ligand proteins useful in treating cancer, neurodegenerative disease, and cardiovascular disease. The recombinant masking proteins provided herein may, inter alia, be used as non-covalent masks of antagonists of, for example, cellular growth factors (e.g., TNF) or cell surface proteins (e.g., CTLA-4).

The present disclosure provides human tear lipocalin muteins that specifically bind to LAG-3, which can be used in pharmaceutical applications, for example, as anti-cancer agents and/or immune modulators for the treatment or prevention of human diseases such as cancer, infectious diseases, and autoimmune diseases. The present disclosure further shows the human lipocalin muteins can inhibit the binding of LAG-3 to MHC class II on cells overexpressing MHC class II. The present disclosure also concerns methods of making LAG-3 binding lipocalin muteins described herein as well as compositions comprising such lipocalin muteins. The present disclosure further relates to nucleic acid molecules encoding such lipocalin muteins and to methods for generation of such lipocalin muteins and nucleic acid molecules. In addition, the application discloses therapeutic and/or diagnostic uses of these lipocalin muteins as well as compositions comprising one or more of such lipocalin muteins.