A nucleic acid molecule comprising a nucleotide sequence encoding an inhibitory chimeric antigen receptor (iCAR) capable of preventing or attenuating undesired activation of an effector immune cell, wherein the iCAR comprises an extracellular domain that specifically binds to a single allelic variant of a polymorphic cell surface epitope absent from mammalian tumor cells due to loss of heterozygosity (LOH) but present at least on all cells of related mammalian normal tissue; and an intracellular domain comprising at least one signal transduction element that inhibits an effector immune cell is provided. Vectors and transduced effector immune cells comprising the nucleic acid molecule and methods for treatment of cancer comprising administering the transduced effector immune cells are further provided.

Antigen binding proteins that specifically recognize a target Melanoma-Associated Antigen A4 (MAGE-A4) peptide-MHC (pMHC), and nucleic acids encoding the same, are provided. Methods of producing antigen binding proteins that specifically recognize a target MAGE-A4 pMHC, and nucleic acid libraries encoding the same, are also provided.

Antibody drug conjugates (ADCs) comprising an antibody conjugated to an anti-inflammatory therapeutic agent via a phosphate-based linker with tunable extracellular and intracellular stability are described.

Fusion polypeptides including at least one Fc binding domain linked to at least one integrin binding domain are provided. In some embodiments, the at least one Fc binding domain is one or more Fc binding domains from Protein A, Protein G, or Protein Z and the at least one integrin binding domain comprises one or more fibronectin type III domains (for example repeats 12-14 of fibronectin type III domains and optionally the connecting segment of fibronectin). Protein complexes including the polypeptide and one or more antibodies are also provided. Methods of using the polypeptide and/or polypeptide:antibody complex are provided, including treating a subject with a tumor, inducing an immune response to a tumor, and/or targeting an antibody to a tumor cell.

The disclosure relates to immune cells for use in adoptive cell therapy that express an inhibitory receptor, useful for treating a disease or disorder, for example, cancer. The disclosure provides immune cells with reduced or eliminated HLA expression, that express an inhibitory receptor, methods of making same, shRNAs targeting HLA-A mRNA, and polynucleotides and vectors encoding same.

The invention relates to compounds, in particular polypeptides that specifically bind to the non-classical MHC protein CD1d and modulate CD1d-mediated biological functions. The invention in particular relates to such compounds and polypeptides comprising or consisting of at least one single domain antibody, and wherein at least one single domain antibody specifically binds to CD1d. Also provided is for methods and use employing such compounds, polypeptides and/or single-domain antibodies.

The present invention relates to T cell receptors (TCRs) that bind the HLA-A*02 restricted peptide GVYDGREHTV (SEQ ID NO: 1) derived from the germline cancer antigen MAGE A4. Said TCRs may comprise non-natural mutations within the alpha and/or beta variable domains relative to a native MAGE A4 TCR. The TCRs of the invention are particularly suitable for use as novel immunotherapeutic reagents for the treatment of malignant disease.

The presently disclosed subject matter provides antigen-binding proteins (e.g., chimeric antigen receptors) and antibodies or antigen-binding portions thereof that bind to a Foxp3 peptide/MHC molecule complex. Such antibodies, fusion proteins and conjugates thereof are useful for inhibiting regulatory T cells and treating cancers.

The present invention relates to peptides, 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 cytotoxic T cell (CTL) peptide epitopes, alone or in combination with other tumor-associated peptides that serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses. The present invention relates to peptide sequences and their variants derived from HLA class I and class II molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses.

The present invention relates to a method for producing a medicament for the treatment or prevention of a tumor in a subject or a diagnostic agent for the detection of a tumor in a subject comprising (A) determining the expression of at least one nucleic acid molecule and/or at least one protein or peptide in a sample obtained from said subject, wherein the at least one nucleic acid molecule is selected from nucleic acid molecules (a) encoding a polypeptide comprising or consisting of the amino acid sequence of any one of SEQ ID NOs 1 to 5, (b) comprising or consisting of the nucleotide sequence of any one of SEQ ID NOs 6 to 10, (c) encoding a polypeptide which is at least 85% identical, preferably at least 90% identical, and most preferred at least 95% identical to the amino acid sequence of (a), (d) consisting of a nucleotide sequence which is at least 95% identical, preferably at least 96% identical, and most preferred at least 98% identical to the nucleotide sequence of (b), (e) consisting of a nucleotide sequence which is degenerate with respect to the nucleic acid molecule of (d), (f) consisting of a fragment of the nucleic acid molecule of any one of (a) to (e), said fragment comprising at least 150 nucleotides, preferably at least 300 nucleotides, more preferably at least 450 nucleotides, and most preferably at least 600 nucleotides, and (g) corresponding to the nucleic acid molecule of any one of (a) to (f), wherein T is replaced by U, and wherein the at least one protein or peptide is selected from proteins or peptides being encoded by the nucleic acid molecule of any one of (a) to (g); and (B) producing a medicament capable of inhibiting the expression of the at least nucleic acid molecule and/or the at least one protein or peptide in the subject, if the at least one nucleic acid molecule and/or at least one protein or peptide is expressed in (A), and/or (B′) producing a diagnostic agent capable of detecting in vivo the sites of expression of the at least nucleic acid molecule and/or the at least one protein or peptide in the subject, if the at least one nucleic acid molecule and/or at least one protein or peptide is expressed in (A).