38 results about "MHC Class II Molecule" patented technology

Combined preparations for the treatment of cancer are described. The combined preparations comprise: (a) LAG-3 protein, or a derivative thereof that is able to bind to MHC class II molecules; and (b) an anti-neoplastic agent, wherein the anti-neoplastic agent is a platinum-based anti-neoplastic agent or a topoisomerase I inhibitor. Methods for the treatment of cancer using the combined preparations are also described.

The present disclosure provides isolated monoclonal antibodies that specifically bind to LAG-3 with high affinity, particularly human monoclonal antibodies. Preferably, the antibodies bind human LAG-3. In certain embodiments, the antibodies bind both human and monkey LAG-3 but do not bind mouse LAG-3. The invention provides anti-LAG-3 antibodies 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 of the invention, expression vectors, host cells and methods for expressing the antibodies of the invention are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. This disclosure also provides methods for detecting LAG-3, as well as methods for treating stimulating immune responses using an anti-LAG-3 antibody of the invention. Combination therapy, in which an anti-LAG-3 antibody is co-administered with at least one additional immunostimulatory antibody, is also provided.

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.

Described herein are methods for treating an autoimmune or inflammatory disease in a patient, comprising administering a composition comprising: a) a plurality of antigen-major histocompatibility class II complexes (antigen-MHCIIs), each antigen-MHCII of the plurality comprising a ubiquitous autoantigen associated with a binding groove of an MHC class II molecule, wherein the ubiquitous autoantigen is chosen from PDC-E2353-367, PDC-E272-86, and PDC-E2422-436 for DRB3*0202; PDC-E2353-367, PDC-E280-94, and PDC-E2535-549 for DRB5*0101; PDC-E2629-648, PDC-E2122-135, and PDC-E2249-263 for DRB4*0101; and PDC-E2249-263 for DRB1*0801; and b) a nanoparticle core possessing a diameter of between 1 and about 100 nanometers; wherein the antigen-MHCs are coupled to the nanoparticle core or a biocompatible layer surrounding the nanoparticle core; and wherein the autoimmune or inflammatory disease is chosen from multiple sclerosis and psoriasis.

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 invention discloses a mouse 4T1 breast cancer therapeutic tumor neoantigen mRNA vaccine and a preparation method and application thereof.The breast cancer therapeutic tumor neoantigen mRNA vaccine comprises an antigen epitope composition, the antigen epitope composition comprises at least one of seven polypeptide fragments combined with MHC class I molecules and three polypeptide fragments combined with MHC class II molecules, and the antigen epitope composition comprises at least one of three polypeptide fragments combined with MHC class II molecules; the amino acid sequences of the seven polypeptide fragments combined with the MHC class I molecules are respectively shown as SEQ ID NO.1-SEQ ID NO.7, and the amino acid sequences of the three polypeptide fragments combined with the MHC class II molecules are respectively shown as SEQ ID NO.8-SEQ ID NO.10. The invention further discloses a preparation method of the polypeptide fragments combined with the MHC class I molecules. The vaccine has an obvious inhibition effect on tumor growth.

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 is directed to the generation of modified mesenchymal stem / stromal cells (MSCs) that express IRF1 in increased levels as compared to the starting MSC source, such as MSC cells lines or primary cells. The cells have the advantage of not only improving their longevity in a variety of settings, such also selectively activating expression of certain therapeutic molecules, such as IDO1 and COX-2, while avoiding problematic induction of signaling pathways such as that involving STAT1 and including MHC class II molecules. These cells are therefore uniquely useful in treating autoimmune diseases and disorders.

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 combined preparations for treating cancers or infections.SOLUTION: Disclosed herein are a combined preparation and a pharmaceutical composition, both comprise: (a) an LAG-3 protein or derivative thereof that can bind to MHC class II molecule; and (b) a programmed cell death protein-1 (PD-1) pathway inhibitor. PD-1 pathway inhibitors, e.g., anti-PD-1 antibodies or anti-PD-L1 antibodies and soluble derivatives of LAG-3 that act as an APC activator, together synergistically activate T cells (in particular, CD8+T cells). Also disclosed are use of the combined preparations and compositions as medicaments, in particular use for treating cancer or infection, as well as a method for treating cancer or infections.SELECTED DRAWING: None

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 invention relates to the technical field of neoantigen screening, and specifically discloses a method for screening neoantigen polypeptide sequences of malignant solid tumors. The method comprises the following steps: obtaining neoantigen prediction results based on HLA class I molecule binding; screening to obtain candidate neoantigen-related mutations; extracting corresponding polypeptide sequences from the neoantigen prediction results to obtain a set of MHC class I potential neoantigen polypeptides; generating all 15-mer sequences centered on the mutation sites and predicting their binding ability to MHC class II molecules to obtain a set of MHC class II potential neoantigen polypeptide sequences; using the maximum margin extension algorithm to obtain long peptide sequences; synthesizing the polypeptide sequences to obtain candidate polypeptide sequences; and evaluating the immunogenicity of the candidate polypeptide sequences to obtain neoantigen polypeptide sequences. The present invention simultaneously considers the binding characteristics of both MHC class I and class II molecules, and can effectively improve the efficiency and accuracy of neoantigen screening.

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.

The present disclosure is based in part on research related to novel tolerogenic peptides derived from proteins expressed by pancreatic cells, developed for use in antigen-specific immunotherapy for type 1 diabetes. Disclosed are tolerogenic peptides that can bind to MHC class II molecules without relying on antigen processing, and are derived from proteins expressed by pancreatic cells, for use in the treatment of type 1 diabetes.

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.

Combined preparations for the treatment of cancer are described. The combined preparations comprise: (a) LAG-3 protein, or a derivative thereof that is able to bind to MHC class II molecules; and (b) an anti-neoplastic agent, wherein the anti-neoplastic agent is a platinum-based anti-neoplastic agent or a topoisomerase I inhibitor. Methods for the treatment of cancer using the combined preparations are also described.

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.

A treatment of an immune-related disease and / or an inflammatory process in an individual by administering a cell composition to a patient, the cell composition including isolated mesenchymal stem cells measured positive for mesenchymal markers CD29, CD44 and CD90 and negative for MHC class II molecules, the cell secretes immunomodulatory prostaglandin E2 cytokine when present in an inflammatory environment or condition.

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.