Disclosed herein are methods and compositions dock and lock (DNL) complexes comprising an AD moiety selected from an AKAP protein and a DDD moiety selected from a protein kinase A regulatory subunit. Also disclosed are fusion proteins comprising an AD moiety or DDD moiety attached to an effector moiety. The DDD moieties form dimers that bind to the AD moiety to form the DNL complexes. The effector moieties may be selected from a wide range of known effector moieties that produce one or more physiological effects, including but not limited to cell death. The DNL complexes may further comprise one or more diagnostic and/or therapeutic agents. The DNL complexes are of use for treating and/or diagnosing a variety of diseases or conditions.

Disclosed in the present invention are a TCR nd an application thereof. The TCR comprises a TCR -chain variable region and/or a TCR -chain variable region. The TCR can specifically recognize and bind to HLA-A*02:01/SLLMWITQC, and is characterized in that the affinity K.sub.D1 of the TCR for the HLA-A*02:01/SLLMWITQC is 0.1-10 M. The TCR can also specifically recognize and bind to one or more of HLA-A*02:03/SLLMWITQC, HLA-A*02:09/SLLMWITQC, HLA-A*02:12/SLLMWITQC, and HLA-A*02:16/SLLMWITQC, and the affinity K.sub.D2 is 0.1-85 M. The TCR in the present invention has extremely high affinity, excellent safety, and wider applicability.

The disclosure relates to immune cells comprising a dual receptor system responsive to loss of heterozygosity in a target cell, and methods of making and using same. The first receptor comprises activator receptor specific to an HLA-E antigen, and the second receptor comprises an inhibitory receptor specific to an antigen lost in cancer but not wild type cells, that inhibits activation of the immune cells by the first receptor.

The present invention relates to compositions comprising transcription factors under control of promoter regions, wherein said compositions can be used for reprogramming cells to type 1 conventional dendritic cells or antigen-presenting cells. The invention further relates to methods for reprogramming cells into type 1 conventional dendritic cells or antigen-presenting cells.

The instant disclosure provides chimeric polypeptides which modulate various cellular processes following a cleavage event induced upon binding of a specific binding member of the polypeptide with its binding partner. Methods of using chimeric polypeptides to modulate cellular functions, including e.g., induction of gene expression, are also provided. Nucleic acids encoding the subject chimeric polypeptides and associated expression cassettes and vectors as well as cells that contain such nucleic acids and/or expression cassettes and vectors are provided. Also provided, are methods of treating a subject using the described components and methods as well as kits for practicing the subject methods.

The instant disclosure provides chimeric polypeptides which modulate various cellular processes following a cleavage event induced upon binding of a specific binding member of the polypeptide with its binding partner. Methods of using chimeric polypeptides to modulate cellular functions, including e.g., induction of gene expression, are also provided. Nucleic acids encoding the subject chimeric polypeptides and associated expression cassettes and vectors as well as cells that contain such nucleic acids and/or expression cassettes and vectors are provided. Also provided, are methods of treating a subject using the described components and methods as well as kits for practicing the subject methods.

Relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL) has a dismal outcome, and no effective targeted immunotherapies for T-ALL exist. CD1a is exclusively expressed in cortical T-ALLs, a major subset of T-ALL. The expression of CD1a is restricted to cortical thymocytes and neither CD34+ progenitors nor T-cells express CD1a during ontogeny, confining the risk of on-target/off-tumor toxicity. The present invention provides CD1a-targeting moieties comprising a CD1a-which may be placed into T cells. The resultant CARTs are suitable for the treatment of cortical T-ALLs.

The present disclosure is directed to methods of modifying an HLA-binding pocket in an HLA molecule in a subject. Some aspects are directed to HLA molecules comprising a modified HLA-binding pocket, where the HLA molecule has increased affinity for a peptide, e.g., an antigen. Other aspects are directed to compositions comprising the same and methods of using the same.

The present disclosure is directed to isolated cell populations comprising stable regulatory T cells and methods of producing the same.

Artificial antigen presenting cells (aAPC) including a major histocompatibility class II (MHC II) molecule and methods of their use for identifying, isolating, or detecting one or more antigen-specific T cells, and treating a disease, disorder, or condition, including cancer, are disclosed.