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Immune Checkpoints and Costimulatory Pathways

 

T cell-mediated immunity is initiated by recognition of antigenic peptide-MHC I/II complexes on antigen presenting cells (APC) through the T cell receptor (TCR).  This transduces an activating signal into the T cells leading to the clonal selection of antigen-specific T cells, subsequently their activation and proliferation in secondary lymphoid organs, their migration to the sites of inflammation, and ultimately the execution of immune effector functions directly or indirectly through other effector cells or factors (e.g., cytokines). T cell responses are regulated by a balance between co-stimulatory and inhibitory signaling pathways elicited by different membrane-bound receptors and ligands (see the diagram below). 

 

 

Above these inhibitory pathways are often referred to as immune checkpoints that are crucial for maintaining self-tolerance (or preventing autoimmunity) as well as modulating the duration and amplitude of immune responses.  Interestingly many immune checkpoint ligands or receptors are overexpressed on tumor cells or on non-transformed cells within the tumor microenvironment.  The blockade of immune checkpoints has been clinically proven to be one of most promising approaches to inducing therapeutic anti-tumor immunity.  For example, anti-CTLA4 monoclonal antibody, Ipilimumab (Yervoy®), and anti-PD1 monoclonal antibodies, Nivolumab (Opdivo®) and Pembrolizumab (Keytruda®), have been approved as a new class of immunotherapy for cancer patients, including those with melanoma and lung cancer (click here to see a list of antibodies in clinical use/development).       

 

Another category of immune-inhibitory molecules or checkpoints include certain metabolic enzymes, such as indoleamine 2,3-dioxygenases (IDO-1, IDO-2), which are expressed by both tumor cells and infiltrating myeloid cells, and arginase (ARG1), which is produced primarily by myeloid-derived suppressing cells.  These enzymes inhibit immune responses through local depletion of amino acids that are essential for anabolic functions in lymphocytes (in particular T cells) or through the synthesis of specific natural ligands for cytosolic receptors that can alter lymphocyte functions.  The molecular analogs of the substrates for above these enzymes can act as competitive inhibitors or suicide substrates that are capable of enhancing intratumoral inflammation and anti-tumor immunity. 

 

 


 

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Immune Checkpoints & Costimulators Related Genes, Proteins and Antibodies

 

G&P Biosciences provide a comprehensive list of products and services for immune checkpoints and co-stimulatory pathways' R&D.  We offer 100% sequence verified full-length cDNA clones for all immune checkpoints and co-stimulators related genes as well as pre-packaged high-titer lentiviral particles for most of them.  The pre-packaged lentiviral particles are ready to transduce any mammalian cell types to generate stable expressing cell lines with the choice of multiple antibiotics selection markers available. We also offer highly purified recombinant proteins (either as a Fc-fusion or with a His-tag) for most immune checkpoints and co-stimulators related gene products.  Additionally we offer recombinant monoclonal antibodies that target immune checkpoint and co-stimulatory molecules with high affinity and specificity.  Many of these antibodies efficiently block immune checkpoint-mediated inhibitory pathways or activate co-stimulatory pathways, therefore potently enhancing anti-tumor immunity in vitro and in vivo.      

 

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Immune Costimulators: Gene, Lentivirus, Protein & Antibody Products

 

  Ligand

  Receptor

  • OX40L: [Gene] [Lentivirus] [OX40L-Fc]
  • 4-1BBL: [Gene] [Lentivirus] [4-1BBL-Fc]
  • CD70: [Gene] [Lentivirus] [CD70-Fc] [anti-CD70]coming soon
  • GITRL: [Gene] [Lentivirus] [GITRL-Fc]
  • CD30L: [Gene] [Lentivirus] [CD30L-Fc]
  • CD40L: [Gene] [Lentivirus] [CD40L-Fc]

 

 

 Immune Checkpoints: Gene, Lentivirus, Protein & Antibody Products

 

  Ligand

   Receptor

  •  GAL9: [Gene] [Lentivirus] [GAL9-Fc]
  •  MHC-I: [Gene] [Lentivirus]
  •  MHC-II: [Gene] [Lentivirus]
  •  LAG3: [Gene] [Lentivirus] [LAG3-Fc] [anti-LAG3]coming soon
  • ?
  • ?
  •  Adenosine
  • A2aR: [Gene] [lentivirus]
  •  Arginine
  • ARG1: [Gene] [lentivirus]
  •  Amino Acid
  • IDO-1: [Gene] [lentivirus]
  •  Amino Acid
  • IDO-2: [Gene] [lentivirus]

 

 

» For more details, please go to our "Gene" "Lentivirus" "Protein" and "Antibody" product pages

» To request a quotation for any custom-made gene, protein or antibody, visit our "Services" pages. 

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