35 results about "PRAME" patented technology

The present application provides a bispecific antibody comprising a first antigen binding fragment that binds to an HLA-A24 / PRAME complex and a second antigen binding fragment that binds to an activated T cell antigen, a single domain antibody that binds to an HLA-A24 / PRAME complex, a pharmaceutical composition comprising the bispecific antibody or the single domain antibody, and uses thereof.

The invention relates to the technical field of biological medicine, in particular to a T cell receptor targeting PRAME peptide and a preparation method of the T cell receptor. Specifically, the invention also provides a T cell receptor, a corresponding nucleic acid molecule, a vector, a host cell and a method for preparing the T cell receptor, and the TCR-T cell obtained by the invention can effectively treat melanoma specific antigen (PRAME) positive tumors and provide more treatment options for patients.

The present invention inter alia relates to an antigen recognizing construct capable of binding to a Preferentially Expressed Antigen in Melanoma (FRAME) peptide, a T cell receptor having antigenic specificity for FRAME, a nucleic acid sequence encoding said antigen recognizing construct or T cell receptor, a vector comprising said nucleic acid sequence, and a host cell comprising said antigen recognizing construct or T cell receptor. The invention also relates to the antigen recognizing construct or T cell receptor, the nucleic acid sequence, vector or host cell for use in medicine or for use in detection, diagnosis, prognosis, prevention and / or treatment of a disease. Additionally, the present invention relates to a method of treating a disease as well as a pharmaceutical composition and a kit.

The invention discloses an antigen binding fragment of an anti-human PRAME protein, a monoclonal antibody as well as preparation and application of the monoclonal antibody. CDR1 of a heavy chain variable region of the antigen binding fragment of the anti-human PRAME protein comprises an amino acid sequence as shown in SEQ ID NO.1, CDR2 comprises an amino acid sequence as shown in SEQ ID NO.2, and CDR3 comprises an amino acid sequence as shown in SEQ ID NO.3; cDR1 of a light chain variable region of the antigen binding fragment of the anti-human PRAME protein comprises an amino acid sequence as shown in SEQ ID NO.4, CDR2 of the light chain variable region of the antigen binding fragment of the anti-human PRAME protein comprises an amino acid sequence as shown in SEQ ID NO.5, and CDR3 of the light chain variable region of the antigen binding fragment of the anti-human PRAME protein comprises an amino acid sequence as shown in SEQ ID NO.6. The monoclonal antibody provided by the invention has high specificity and low cross reactivity, can efficiently and specifically recognize natural and denatured PRAME proteins, and is suitable for immunological detection, especially immunohistochemical detection.

The present invention relates to combinations of host cells expression antigen binding proteins that specifically bind to a tumor expressed Preferentially Expressed Antigen of Melanoma (PRAME) antigenic peptide in a complex with MHC, and mRNAs encoding PRAME antigenic peptides. The invention further relates to combined TCR-T / mRNA therapy employing said mRNAs and host cells. In particular, a combined TCR-T / mRNA therapy is provided for use in cancer treatment.

This disclosure provides for engineered T cell Receptors (TCRs), cells comprising the TCRs, and methods of making and using the TCRs. The current disclosure relates to TCRs that specifically recognize epitope(s) from tumor antigen PRAME. Accordingly, the disclosure relates to engineered T-cell Receptors (TCRs), nucleic acids encoding the TCRs, and cells comprising the nucleic acids and TCRs. Also provided are compositions comprising the cells, nucleic acids, or engineered TCRs of the disclosure, methods of making the cells and methods of using the embodiments of the disclosure for therapeutic treatments.

Provided herein are activated adoptive T-cell compositions targeting plasma cell dyscrasias such as multiple myeloma and methods of treating plasma cell dyscrasias such as multiple myeloma using such compositions. The T-cell compositions of the present disclosure are activated against a select group of antigens associated with multiple myeloma (MMAAs) and, in certain embodiments, in combination with more widely expressed tumor associated antigens (TAAs). In particular, the T-cell compositions of the present disclosure are directed to the MMAAs selected from B-cell maturation antigen (BCMA), X box Protein 1 (XBP1), CS1, and Syndecan-1 (CD138), or a combination thereof. In certain embodiments, the T-cell composition includes T-cells activated to a TAA selected from preferentially expressed antigen of melanoma (PRAME), Survivin, Wilms' Tumor 1 protein (WT1), and melanoma antigen 3 (MAGE-A3), or a combination thereof.

Provided are a bispecific antibody comprising a first antigen-binding fragment that binds to an HLA-A24 / PRAME complex and a second antigen-binding fragment that binds to an activated T-cell antigen, a single-domain antibody that binds to an HLA-A24 / PRAME complex, and a pharmaceutical composition comprising the bispecific antibody or the single-domain antibody. Also provided is the use of the bispecific antibody or the single-domain antibody in medicine and biology.

Provided are recombinant polypeptides, pharmaceutical compositions and uses thereof, and methods of preventing or treating cancer. The recombinant polypeptide comprises a first subunit comprising all or a fragment of an amino acid sequence of programmed death-ligand 1 (PD-L1) and a second subunit comprising all or a fragment of an amino acid sequence of preferentially expressed antigen in melanoma (PRAME). The dual-antigen cancer vaccines co-targeting PD-L1 and PRAME are effective in preventing, improving, or treating cancer and / or suppressing tumor growth prophylactically and therapeutically.

To provide PRAME-binding molecules having moderate affinity for HLA-A24PRAMEp301-309pMHC complexes and high recognition specificity.SOLUTION: PRAME binding molecules comprising a heavy chain CDR1, a heavy chain CDR2, and a heavy chain variable region comprising the heavy chain CDR3, each comprising a specific amino acid sequence, and / or a light chain CDR1 comprising a specific amino acid sequence, a light chain CDR2 comprising the amino acid sequence GKN, and a light chain variable region comprising the light chain CDR3, each comprising a specific amino acid sequence.SELECTED DRAWING: None

The present invention provides isolated T cell receptors (TCRs) that specifically bind to an HLA-displayed cancer testis antigen preferentially expressed antigen in melanoma (FRAME) peptide, as well as therapeutic and diagnostic methods of using those isolated TCRs.

To enable detection of urothelial cancer, to provide a diagnostic marker for urothelial cancer, to enable prediction as to whether a patient is resistant to BCG therapy, and to provide a BCG therapy resistance marker.SOLUTION: Methods of detecting urothelial cancer diagnostic marker and / or BCG therapy resistance marker are provided, the methods comprising a step of detecting PRAME of a sample collected from a subject, where the sample is of a urothelial tumor or of urinary cells.SELECTED DRAWING: None

Provided herein are PRAME immunogenic peptides, binding proteins that recognize PRAME immunogenic peptides, and uses thereof. The present invention is based, at least in part, on the discovery of PRAME immunogenic peptides and binding proteins that recognize such PRAME immunogenic peptides based on unbiased functional selection methods used to discover antigens of TCR clonotypes identified from subjects with disorders associated with PRAME expression (e.g., subjects suffering from melanoma, head and neck cancer, lung cancer, leukemia (e.g., leukemia subtypes), ovarian cancer, renal cell carcinoma (RCC), breast cancer, cervical cancer, or colon cancer, sarcoma, and neuroblastoma).

To provide a medical preparation for treatment of ovarian cancers.SOLUTION: In one aspect, a composition or a medical preparation comprising at least one RNA is provided, wherein the at least one RNA encodes the following amino acid sequences: (i) an amino acid sequence comprising claudin 6 (CLDN6), an immunogenic variant thereof, or an immunogenic fragment of the CLDN6 or the immunogenic variant thereof; (ii) an amino acid sequence comprising p53, an immunogenic variant thereof, or an immunogenic fragment of the p53 or the immunogenic variant thereof; and (iii) an amino acid sequence comprising Preferentially Expressed Antigen in Melanoma (PRAME), an immunogenic variant thereof, or an immunogenic fragment of the PRAME or the immunogenic variant thereof.SELECTED DRAWING: None

Provided herein are PRAME immunogenic peptides, binding proteins that recognize PRAME immunogenic peptides, and uses thereof.

Provided are recombinant polypeptides, pharmaceutical compositions and uses thereof, and methods of preventing or treating cancer. The recombinant polypeptide comprises a first subunit and a second subunit, the first subunit comprises all or fragments of the amino acid sequence of programmed death ligand 1 (PD-L1), and the second subunit comprises all or fragments of the amino acid sequence of a melanoma preferential expression antigen (PRAME). The dual antigen cancer vaccine co-targeting PD-L1 and PRAME effectively prevents, ameliorates or treats cancer and / or inhibits tumor growth in the prophylactic and therapeutic aspects.

The present invention relates to the field of biomedicine, and in particular to T cell receptors targeting the PRAME peptide and methods for preparing the same. Specifically, the present application also provides T cell receptors, corresponding nucleic acid molecules, vectors, and host cells, as well as methods for preparing T cell receptors. The TCR-T cells obtained in the present application can effectively treat melanoma-specific antigen (PRAME)-positive tumors, providing patients with more treatment options.

The present disclosure relates to genetically modified arenaviruses suitable for the treatment of neoplastic diseases, such as cancer. The arenaviruses described herein may be suitable for treatment of neoplastic diseases and / or for the use in immunotherapies. In particular, provided herein are methods and compositions for treating a neoplastic disease by administering a genetically modified arenavirus, wherein the arenavirus has been engineered to include a nucleotide sequence encoding one or more antigenic fragment(s) of one or more cancer testis antigens (CTAs), including members of the melanoma-associated antigen (MAGE) family and preferentially expressed antigen in melanoma (PRAME). Specifically, provided herein is a genetically modified arenavirus, wherein the arenavirus has been engineered to include a nucleotide sequence encoding antigen fragments and / or epitopes of PRAME, MAGE-A3, MAGE-A4 and MAGE-A6.

To provide T cell receptor for the antigen primarily expressed in melanoma (PRAME) and use methods thereof.SOLUTION: The invention provides isolated T cell receptors (TCRs) that specifically bind to an antigen peptide preferentially expressed in melanoma (PRAME) peptide being an HLA presented cancer testis antigen, as well as therapeutic and diagnostic methods using the isolated TCRs. The invention provides T cell receptors (TCRs) that are generated against a PRAME peptide antigen in the context of MHC (HLA-A2). The identified unique TCR sequences show specific binding to a small peptide PRAME presented in the groove of an HLA molecule.SELECTED DRAWING: None

The present disclosure relates to T cell receptors (TCRs) capable of binding to HLA-A * 02 restrictive peptides derived from PRAME. The disclosure also relates to complexes comprising the TCRs, nucleic acids and vectors encoding the TCRs or portions thereof, cells comprising the TCRs, pharmaceutical compositions, and methods of using the TCRs to treat diseases, such as cancer.

The present invention concerns antigen binding proteins directed against PRAME protein-derived antigens. The invention in particular provides antigen binding proteins which are specific for the tumor expressed antigen PRAME, wherein the tumor antigen comprises or consists of SEQ ID NO: 50 and is in a complex with a major histocompatibility complex (MHC) protein. The antigen binding proteins of the invention contain, in particular, the complementary determining regions (CDRs) of novel engineered T cell receptors (TCRs) that specifically bind to said PRAME peptide. The antigen binding proteins of the invention are for use in the diagnosis, treatment and prevention of PRAME expressing cancerous diseases. Further provided are nucleic acids encoding the antigen binding proteins of the invention, vectors comprising said nucleic acids, recombinant cells expressing the antigen binding proteins and pharmaceutical compositions comprising the antigen binding proteins of the invention.

Described herein are antigen binding proteins targeting FRAME derived peptide- MHCs (pMHCs). Also described are multispecific antigen binding proteins comprising an antigen binding domain with specificity to CD3, and at least one target peptide binding domain, in particular bispecific antigen binding proteins targeting both CD3 and FRAME. Methods of treatment with the same are also described.

The compositions and methods described herein are directed to treating solid tumors using CAR T therapy. For example, the compositions include CAR T cells comprising an extracellular domain that binds OR2I1P, LY6G6D, LRRC15, LY6K, GCC, GFRA4, F2RL2, QRFPR, IQGAP3, SIGLEC15, HAVCR1, PSG9, KISS1R, PRAME, HCN4, DPEP3, TMEM270, HER2, SLC7A3, SPRR2F, SLC45A2, CHRM1, CHRNA2, STEAP1B, FCRL2, Luteinizing hormone receptor, EDB, or CLDN18.2.

Present disclosure provides engineered polynucleotides encoding concatemeric FRAME epitope polypeptides, including concatemeric FRAME epitope polypeptides capable of promoting an immune response to cancer cells expressing FRAME. The disclosure also provides pharmaceutical compositions and kits comprising the same, and methods of use and treatment of PRAME-positive cancers.

Provided herein are novel nucleic acid compositions, vector systems, engineered cells, and pharmaceutical compositions that encode or express T cell receptor components against cancer-associated antigens (e.g., preferentially expressed melanoma antigen (PRAME) and CCCTC-binding factor (CTCFL)). These novel compositions may be used to enhance immune responses in subjects diagnosed with a PRAME-associated disease or condition, such as a hematological malignancy or solid tumor, or a CTCFL-associated disease or condition. Related methods for treating such subjects are also provided herein.

A single-domain antibody targeting a PRAME polypeptide. The single-domain antibody targeting the PRAME polypeptide can bind to the PRAME polypeptide with high affinity and has relatively good specificity, thereby laying a new material foundation for the development of an anti-tumor drug targeting the PRAME polypeptide. Further disclosed are a bispecific antibody, a chimeric antigen receptor, a chimeric antigen receptor-T cell, an ADC, etc., prepared by means of using the single-domain antibody.

Aspects of the application provide composition (e.g., anti-PRAME / HLA-A2 antibodies, and / or anti-PRAME / A2xT cell bispecific antibodies) and methods of using the same in treating cancer (e.g., cancer expressing PRAME).

The present invention relates to a T cell receptor (TCR) capable of binding to a PRAME peptide having the amino acid sequence SLLQHLIGL (SEQ ID NO: 1) or a portion thereof, or its HLA-A2 bound form. Also encompassed in the present invention is a nucleic acid encoding a TCR, a vector comprising the nucleic acid, and a host cell comprising the TCR, the nucleic acid sequence, or the vector. Comprised is further, a method for obtaining a TCR described herein, a pharmaceutical or diagnostic composition, and a method of detecting the presence of a cancer in a subject in vitro. Furthermore, the present invention relates to the use of a TCR, a nucleic acid and / or a vector for generating modified lymphocytes.