26 results about "MHC Class II Molecule" patented technology

Treatment of Cancer Methods for treatment of cancer, in particular soft tissue sarcomas (STS), are described, as well as compounds, compositions, and combined preparations for use in such methods. An effective amount of: a LAG-3 protein, or a derivative thereof that is able to bind to MHC class II molecules; a programmed cell death protein-1 (PD-1) pathway inhibitor; and radiotherapy, is administered to a subject. Optionally the subject has undergone, is undergoing, or is to undergo, surgery for treatment of the cancer. A clinical trial study is described in which a triple combination of LAG-3 derivative eftilagimod alpha, a PD-1 pathway inhibitor, and radiotherapy was administered. The combination was surprisingly effective in the treatment of STS in patients who have completed 10 weeks of treatment, followed by surgery 2-3 weeks later. A substantial number of near complete pathological responses were observed, which are rarely seen in STS patients with standard therapeutic approaches including radiotherapy.

The present disclosure is directed to HLA class II molecules having a higher affinity for CD4 than naturally occurring HLA class II molecules. In certain aspects, the HLA class II molecule comprises a DQ beta chain having (i) an amino acid other than leucine at a position corresponding to amino acid residue 114 of SEQ ID NO: 1, (ii) an amino acid other than valine at a position corresponding to amino acid residue 143 of SEQ ID NO: 1, (iii) or both (i) and (ii). Certain aspects of the present disclosure are directed to nucleic acid molecules encoding the HLA class II molecules, vectors comprising the nucleic acid molecule, cells comprising the same, and methods of use thereof.

The present disclosure is based in part on studies on novel tolerogenic peptides derived from a protein expressed by a pancreatic cell, which have been developed for use in antigen-specific immunotherapy for type 1 diabetes. Disclosed is a tolerogenic peptide capable of binding an MHC class II molecule independent of antigen processing for use in the treatment of type 1 diabetes, wherein the peptide is derived from a protein expressed by a pancreatic cell.

The present disclosure relates to HLA class II molecules having higher affinity for CD4 than naturally occurring HLA class II molecules. In certain aspects, the HLA class II molecules comprise a DQ beta chain having: (i) an amino acid other than leucine at a position corresponding to amino acid residue 114 of SEQ ID NO: 1, (ii) an amino acid other than valine at a position corresponding to amino acid residue 143 of SEQ ID NO: 1, or (iii) both (i) and (ii). Certain aspects of the present disclosure relate to nucleic acid molecules encoding the HLA class II molecules, vectors comprising the nucleic acid molecules, cells comprising them, and methods of using the same.

The present disclosure relates to HLA class II molecules having higher affinity for CD4 than naturally occurring HLA class II molecules. In certain aspects, the HLA class II molecules comprise a DR beta chain having: (i) an amino acid other than leucine at a position corresponding to amino acid residue 114 of SEQ ID NO: 1, (ii) an amino acid other than valine at a position corresponding to amino acid residue 143 of SEQ ID NO: 1, (iii) or both (i) and (ii). Certain aspects of the present disclosure relate to nucleic acid molecules encoding the HLA class II molecules, vectors comprising the nucleic acid molecules, cells comprising them, and methods of using the same.

The present disclosure relates to HLA class II molecules having higher affinity for CD4 than naturally occurring HLA class II molecules. In certain aspects, the HLA class II molecules comprise a DP beta chain having: (i) an amino acid other than leucine at a position corresponding to amino acid residue 112 of SEQ ID NO: 1, (ii) an amino acid other than valine at a position corresponding to amino acid residue 141 of SEQ ID NO: 1, or (iii) both (i) and (ii). Certain aspects of the present disclosure relate to nucleic acid molecules encoding the HLA class II molecules, vectors comprising the nucleic acid molecules, cells comprising them, and methods of using the same.

The present disclosure relates to methods of identifying MHC class II specific T cell receptors (TCRs). In certain aspects, the methods comprise contacting a T cell with a complex comprising (i) an MHC class II molecule having a higher affinity for CD4 than a naturally occurring MHC class II molecule, and (ii) a peptide, e.g., an epitope. In certain aspects, the HLA class II molecule comprises a beta chain having one or more mutations relative to a wild-type beta chain sequence.

To provide methods of identifying T cell receptors.SOLUTION: The present disclosure is directed to methods of identifying MHC class II-specific T cell receptors (TCRs). In certain aspects, the method comprises contacting a T cell with a complex comprising (i) an MHC class II molecule having a higher affinity for CD4 than naturally occurring MHC class II molecules and (ii) a peptide, e.g., an epitope. In certain aspects, the HLA class II molecule comprises a beta chain having one or more mutations relative to a wild-type beta chain sequence.SELECTED DRAWING: None

The present disclosure provides nucleic acid molecules (e.g., a plasmid or vector) comprising a nucleic acid sequence encoding a bicistronic or multicistronic LAMP Construct comprising specific fragments of the LAMP luminal domain and an antigenic domain heterologous to the LAMP protein to provide at least one antigen for priming an immune response, wherein the antigen expressed by the Construct is optionally processed and presented to MHC class II molecules, and also a nucleic acid sequence encoding an immune response enhancing polypeptide that is optionally secreted from a host cell. The nucleic acid molecules can be used, for example, for the treatment of disease and in particular, allergies, infectious disease, diabetes, hyperproliferative disorders and / or cancer.

To provide cells having reduced immunogenicity and methods for producing such cells, compositions, and methods for treating kidney disease, to provide regenerative effects to a native kidney for the treatment of chronic kidney disease.SOLUTION: Provided herein are: bioactive renal cells (BRCs) in which a gene encoding a protein within a major histocompatibility complex (MHC) class I molecule or a MHC class II molecule is modified; and methods for producing the same. The genetically modified BRC comprises a heterologous polynucleotide (for example, a plasmid or a viral vector) that expresses an RNA interference (RNAi) molecule that reduces expression of the gene in the BRC.SELECTED DRAWING: Figure 10

The invention provides a chicken Marek's virus (MHC) II type molecule restriction epitope peptide, a gene, a primer group, a screening method and application, and belongs to the technical field of immunology. The restrictive epitope peptide of the II-type molecule BLB2 * 21 of the chicken Marek's virus MHC is obtained through AF3 structure prediction and screening, the deviation of traditional bioinformatics prediction is avoided, and the binding activity of the epitope peptide is guaranteed through accurate structure analysis and crystallization verification; the gene for coding the chicken Marek's virus MHC II type molecule restrictive epitope peptide can be used for preparing Marek's virus epitope vaccines and T cell activators, or can be used as a detection target for evaluating the immune state of chicken flocks, and technical support is provided for Marek's disease prevention and control, disease resistance breeding and novel vaccine research and development.

The present disclosure provides nucleic acid molecules (e.g., a plasmid or vector) comprising a nucleic acid sequence encoding a bicistronic or multicistronic LAMP Construct comprising specific fragments of the LAMP luminal domain and an antigenic domain heterologous to the LAMP protein to provide at least one antigen for priming an immune response, wherein the antigen expressed by the Construct is optionally processed and presented to MHC class II molecules, and also a nucleic acid sequence encoding an immune response enhancing polypeptide that is optionally secreted from a host cell. The nucleic acid molecules can be used, for example, for the treatment of disease and in particular, allergies, infectious disease, diabetes, hyperproliferative disorders and / or cancer.

Disclosed is a method for identifying peptides, which are bound and / or presented by MHC class I and / or MHC class II molecules in an individual, where the method utilises a transformer encoder-decoder model comprising an artificial neural network (ANN) architecture, wherein the transformer encoder receives as input MHC molecule amino acid sequence of a peptide:MHC data pair and outputs a high-dimensional representation of the MHC amino acid sequence, wherein the transformer decoder receives the high-dimensional representation of the MHC molecule amino acid sequence and the peptide amino acid sequence of a peptide:MHC data pair with residue embedding and positional encoding as input and outputs a high-dimensional representation of the relationship between the MHC molecule amino acid sequence and the peptide sequence, and wherein the output from the transformer decoder is used to calculate a quantitative assessment of the ability of the MHC molecule to bind and / or present the peptide. Also disclosed is a method of training the model, a computer or computer system adapted to carry out the method, and a method of identifying MHC binding amino acid sequence derived from proteins.

The present disclosure is directed to HLA class II molecules having a higher affinity for CD4 than naturally occurring HLA class II molecules. In certain aspects, the HLA class II molecule comprises a DP beta chain having (i) an amino acid other than leucine at a position corresponding to amino acid residue 112 of SEQ ID NO: 1, (ii) an amino acid other than valine at a position corresponding to amino acid residue 141 of SEQ ID NO: 1, (iii) or both (i) and (ii). Certain aspects of the present disclosure are directed to nucleic acid molecules encoding the HLA class II molecules, vectors comprising the nucleic acid molecule, cells comprising the same, and methods of use thereof.

The present disclosure relates to HLA class II molecules that have a higher affinity for CD4 than naturally occurring HLA class II molecules. In certain embodiments, the HLA class II molecules comprise a DR beta chain having (i) an amino acid other than leucine at the amino acid residue corresponding to position 114 of SEQ ID NO: 1, (ii) an amino acid other than valine at the amino acid residue corresponding to position 143 of SEQ ID NO: 1, or (iii) both (i) and (ii). Certain embodiments of the present disclosure relate to nucleic acid molecules encoding the HLA class II molecules, vectors comprising the nucleic acid molecules, cells comprising the vectors, and methods of use thereof.

The present disclosure is directed to HLA class II molecules having a higher affinity for CD4 than naturally occurring HLA class II molecules. In certain aspects, the HLA class II molecule comprises a DR beta chain having (i) an amino acid other than leucine at a position corresponding to amino acid residue 114 of SEQ ID NO: 1, (ii) an amino acid other than valine at a position corresponding to amino acid residue 143 of SEQ ID NO: 1, (iii) or both (i) and (ii). Certain aspects of the present disclosure are directed to nucleic acid molecules encoding the HLA class II molecules, vectors comprising the nucleic acid molecule, cells comprising the same, and methods of use thereof.

Combined preparations, and pharmaceutical compositions, comprising: (a) LAG-3 protein, or a derivative thereof that is able to bind to MHC class II molecules; and (b) a programmed cell death protein-1 (PD-1) pathway inhibitor, are described. The PD-1 pathway inhibitor, such as an anti-PD-1 antibody or an anti-PD-L1 antibody, and a soluble derivative of LAG-3, acting as an APC activator, together synergistically activate T cells (in particular, CD8+ T cells). Use of the combined preparations and compositions as medicaments, in particular for the treatment of cancer or infection, and to methods for the treatment of cancer or infection, is described.

Provided is a new composition capable of inducing an immune response against a target antigen. A composition according to the present disclosure comprises: a target antigen or a polynucleotide encoding the same; and an expression inducer of major histocompatibility gene complex class II (MHC class II molecule) and / or an expression inhibitor of an invariant chain thereof.

The invention relates to a tolerogenic polypeptide capable of binding to an MHC Class II molecule independent of antigen processing, which is derived from Der p 1, and its uses in the treatment or prevention of an allergy. The invention also relates to method of treating or preventing an allergy in a subject in need thereof, comprising administering to the subject a therapeutically affective amount of the tolerogenic polypeptide.

The present disclosure relates to HLA class II molecules that have a higher affinity for CD4 than naturally occurring HLA class II molecules. In certain embodiments, the HLA class II molecules comprise a DQ beta chain having (i) an amino acid other than leucine at the amino acid residue corresponding to position 114 of SEQ ID NO: 1, (ii) an amino acid other than valine at the amino acid residue corresponding to position 143 of SEQ ID NO: 1, or (iii) both (i) and (ii). Certain embodiments of the present disclosure relate to nucleic acid molecules encoding the HLA class II molecules, vectors comprising the nucleic acid molecules, cells comprising the vectors, and methods of use thereof.

The present disclosure is directed to HLA class II molecules having a higher affinity for CD4 than naturally occurring HLA class II molecules. In certain aspects, the HLA class II molecule comprises a DQ beta chain having (i) an amino acid other than leucine at a position corresponding to amino acid residue 114 of SEQ ID NO: 1, (ii) an amino acid other than valine at a position corresponding to amino acid residue 143 of SEQ ID NO: 1, (iii) or both (i) and (ii). Certain aspects of the present disclosure are directed to nucleic acid molecules encoding the HLA class II molecules, vectors comprising the nucleic acid molecule, cells comprising the same, and methods of use thereof.

Compositions comprising an MHC ligand peptide covalently attached to an MHC class II molecule are provided herein. In some compositions, the MHC ligand peptide is covalently attached to the MHC class II molecule by a peptide linker, wherein the MHC ligand peptide or the peptide linker comprises a first cysteine, wherein the MHC class II a chain or a portion thereof or the MHC class II β chain or a portion thereof comprises a second cysteine, and wherein the first cysteine and the second cysteine form a disulfide bond such that the MHC ligand peptide is bound in a peptide-binding groove formed by the MHC class II a chain or the portion thereof and the MHC class II β chain or the portion thereof. Also provided are nucleic acids encoding such compositions and methods for using such compositions to elicit an immune response in a subject.

The present disclosure provides isolated human monoclonal antibodies and antigen-binding fragments thereof that bind to human LAG-3, particularly antibodies and antigen-binding antibody fragments that can inhibit the binding of LAG-3 to MHC Class II molecules and that can stimulate antigen-specific T cell responses. Nucleic acid molecules encoding the antibodies and antigen-binding fragments of the invention as well as compositions and immunoconjugates of the antibodies and antigen-binding antibody fragments of the invention are also provided. This disclosure also provides for the use of the antibodies and antigen-binding antibody fragments of the invention in therapy.

The present invention relates to a method for activating helper T cells, which includes the step of activating helper T cells by adding a WT1 peptide to antigen presenting cells, wherein the WT1 peptide has the ability to bind to any MHC class II molecule of an HLA-DRB1*0101 molecule, an HLA-DRB1*0401 molecule, an HLA-DRB1*0403 molecule, an HLA-DRB1*0406 molecule, an HLA-DRB1*0803 molecule, an HLA-DRB1*0901 molecule, an HLA-DRB1*1101 molecule, an HLA-DRB3*0202 molecule, an HLA-DRB4*0101 molecule, an HLA-DPB1*0201 molecule or an HLA-DPB1*0301 molecule, and the like.

To provide a peptide-MHC II protein construct and use of the construct.SOLUTION: Provided is a composition includes an MHC ligand peptide covalently bonded to an MHC class II molecule. In several compositions, the MHC ligand peptide is covalently bonded to the MHC class II molecule by a peptide linker, the MHC ligand peptide or peptide linker includes first cysteine, an MHC class IIα chain or a part thereof or an MHC class IIβ chain or a part thereof includes second cysteine, the first cysteine and the second cysteine form disulfide bond such that the MHC ligand peptide bonds in a peptide-binding groove formed of the MHC class IIα chain or a part thereof and the MHC class IIβ chain or a part thereof.SELECTED DRAWING: None

Triple Combination Therapy A triple combination therapy for the treatment of cancer is described. The treatment comprises use of a LAG-3 protein, or a derivative thereof that is able to bind to MHC class II molecules, a programmed cell death protein-1 (PD-1) pathway inhibitor, and a chemotherapy agent. The LAG-3 protein, or a derivative thereof, is to be administered simultaneously or sequentially with the PD-1 pathway inhibitor and chemotherapy agent. The triple combination improves overall survival (OS), overall response rate (ORR), disease control rate (DCR), or progression-free survival (PFS), of a subject with a cancer, in particular with non-small cell lung cancer (NSCLC). Methods of treatment are also described.