38 results about "BTLA" patented technology

The present invention provides a novel lymphocyte inhibitory receptor termed BTLA which is expressed on both T and B cells, and identifies B7 family member B7x as interacting with BTLA to attenuate lymphocyte activity. Methods and compositions for modulating BTLA-mediated negative signaling and interfering with the interaction of BTLA and B7x for therapeutic, diagnostic and research purposes are also provided.

This disclosure provides a multi-specific fusion protein composed of a CD86 antagonist binding domain and another binding domain that is an IL-10 agonist, an HLA-G agonist, an HGF agonist, an IL-35 agonist, a PD-1 agonist, a BTLA agonist, a LIGHT antagonist, a GITRL antagonist or a CD40 antagonist. The multi-specific fusion protein may also include an intervening domain that separates the other domains. This disclosure also provides polynucleotides encoding the multi-specific fusion proteins, compositions of the fusion proteins, and methods of using the multi-specific fusion proteins and compositions.

The present invention relates to binding compounds specific for BTLA and uses thereof. More specifically, the invention relates to fully human antibodies that recognize human BTLA and modulate its activity in cancer, inflammatory, and autoimmune disorders.

The invention provides HVEM cis complexes which include, for example, HVEM/BTLA, HVEM/CD160 and HVEM/gD cis complexes. The invention provides ligands and agents that bind to HVEM cis complexes, such as antibodies. The invention further provides methods of use of the HVEM cis complexes, and the ligands and agents (e.g., LIGHT polypeptide sequence) that bind to the HVEM cis complexes.

The present disclosure provides isolated monoclonal antibodies, particularly human monoclonal antibodies that specifically bind to BTLA with high affinity. Nucleic acid molecules encoding the antibodies of the disclosure, expression vectors, host cells and methods for expressing the antibodies of the disclosure are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the disclosure are also provided. The disclosure also provides methods for detecting BTLA, as well as methods for treating various diseases, including cancer and infectious diseases, using anti-BTLA antibodies.

The invention provides a group of markers for predicting the storm of an immune checkpoint of COVID-19, application, a kit and a preparation method of the kit, which belong to the technical field of biological medicines. The markers provided by the invention comprise one or more than two of BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, TIM-3, CD28, CD80, 4-1BB, CD27 and CD152. When the biomarker or the kit prepared from the biomarker provided by the invention is used for predicting the storm of the immune checkpoint of the COVID-19, the biomarker or the kit has the advantages of rapidness and accuracy in detection, low cost and the like, and has a wide application prospect.

The invention discloses a preparing method of BTLA<-/->T lymphocytes resistant to the tumor immunosuppression environment. The preparing method includes the steps that T lymphocytes are obtained through separation from peripheral blood of a tumor patient, BTLA is subjected to gene knockout in vitro with the CRISPR-Cas9 technology, then the obtained T lymphocytes are put into a serum-free medium and cultured, IFN-gamma, a CD3 monoclonal antibody, IL-2, IL-1alpha, IL-4, GM-CSF and Puromycin are added, the obtained T lymphocytes continue to be cultured for 10 days to 15 days, then centrifugationis carried out, and the BTLA<-/->T lymphocytes are obtained. The preparing method of the BTLA<-/->T lymphocytes is ingenious in design, the BTLA<-/->T lymphocytes prepared with the method have the characteristic resistant to the tumor immunosuppression environment, and have the better tumor killing effect, the clinical effect is improved, and a novel anti-tumor and tumor treatment mean is provided.

Some embodiments of the disclosure use human peripheral blood for ctDNA sequencing or tumor tissues for whole exome sequencing, screen out mutation sites to perform antigen epitope prediction, connect and synthesize an expression gene sequence of mutant peptides. Other embodiments of the disclosure construct a lentiviral vector, package the lentivirus, transfect an APC cell to complete transformation of a specific LV cell, co-culture in vitro with PBMC separated from the peripheral blood, screen out an effective polypeptide, and transform common T cells into RFF cells. Suppressive signaling molecules include one or more of PD-1, Tim-3, LAG3, CTLA-4, BTLA, VISTA, CD160, and 2B4 (CD244). Antigen presenting cells include one or more of PBMC, a dendritic cell, neutrophil, B lymphocyte, and macrophage.

The present invention is based on the seminal discovery that BTLA agonist fusion proteins modulate an immune response. Specifically, the present invention provides fusion proteins that bind BTLA enhancing BTLA signaling The present invention further provides methods of treating cancer and immune and inflammatory diseases and disorders with a BTLA agonist fusion protein as described herein.

The invention discloses a pluripotent stem cell for expressing shRNA (short hairpin Ribonucleic Acid) and/or shRNA-miR (short hairpin Ribonucleic Acid-miR) targeting BTLA (Bacterial Type Leukocyte Antigen) or a derivative of the pluripotent stem cell. An expression sequence of the shRNA and/or the shRNA-miR targeting BTLA is introduced into a genome of the pluripotent stem cell or the derivative of the pluripotent stem cell. After shRNA (short hairpin ribonucleic acid) and/or shRNA-miR (short hairpin ribonucleic acid-miR) of targeted BTLA expressed by the pluripotent stem cell or the derivative of the pluripotent stem cell provided by the invention is wrapped by exosome, the exosome carries the effect RNA molecules to be combined with target cells, and then the target cells are released, so that BTLA is blocked, immunosuppression is relieved, an immune system is activated, the activity of T cells is recovered, and the T cells can effectively remove tumor cells.

The invention relates generally to antibodies or antigen binding fragments that bind to human B and T lymphocyte attenuator (BTLA) and uses thereof. More specifically, the invention relates to agonistic antibodies that bind human BTLA and modulate its activity, and their use in treating inflammatory, autoimmune and proliferative diseases and disorders.

The invention provides novel anti-BTLA antibodies, pharmaceutical compositions comprising such antibodies, and therapeutic methods of using such antibodies and pharmaceutical compositions for the treatment of diseases such as cancer or autoimmune disease.