|44689T||1 Kit (9 x 20 microliters)||
|PD-1 (Intracellular Domain) (D4W2J) XP® Rabbit mAb 86163||20 µl||
|TIM-3 (D5D5R™) XP® Rabbit mAb 45208||20 µl||
|LAG3 (D2G4O™) XP® Rabbit mAb 15372||20 µl||
|VISTA (D1L2G™) XP® Rabbit mAb 64953||20 µl||
||H Mk||45-65||Rabbit IgG|
|B7-H3 (D9M2L) XP® Rabbit mAb 14058||20 µl||
|4-1BB/CD137/TNFRSF9 (D2Z4Y) Rabbit mAb 34594||20 µl||
||H||32, 40||Rabbit IgG|
|OX40 (E9U7O) XP® Rabbit mAb 61637||20 µl||
||H M R||35-50||Rabbit IgG|
|GITR (D9I9D) Rabbit mAb 68014||20 µl||
|CD40 Ligand (D5J9Y) Rabbit mAb 15094||20 µl||
||H||25-30 (membrane bound); 17 (soluble)||Rabbit IgG|
Monoclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Ala274 of human PD-1 protein, Gln264 of human OX40 protein, Val142 of human GITR protein, Ala94 of human B7-H3 protein, or near the carboxy terminus of human VISTA protein. Monoclonal antibodies are produced by immunizing animals with a recombinant protein specific to the extracellular domain of human TIM-3 protein, human 4-1BB/CD137/TNFRSF9 protein, human CD40 ligand protein, or the amino terminus of human LAG3 protein.
PD-1 (PDCD1, CD279), TIM-3 (HAVCR2), LAG3 (CD223), VISTA (PD-H1), and B7-H3 (CD276) are immune cell co-inhibitory receptors (also known as immune checkpoints) that negatively regulate T cell function, and dampen the immune response to pathogens and cancer. In addition to activated T cells, PD-1 is expressed by activated B-cells and monocytes. TIM-3 is expressed by exhausted T cells in the settings of chronic infection and cancer. Tumor-infiltrating macrophages and dendritic cells also express TIM-3. LAG3 is primarily expressed by activated CD4+ T cells, CD8+ T cells, FoxP3+ T regulatory cells (Tregs) and natural killer (NK) cells. Although primarily expressed by myeloid cells, VISTA is also expressed by CD4+, CD8+, and Treg cells. Research examining the biological function of B7-H3 suggested that B7-H3 can be both a positive and negative regulator of T cell response. B7-H3 is expressed by antigen presenting cells, activated T cells, and a few normal tissues, including placenta and prostate. Expression of B7-H3 is seen in several cancer types, including prostate, breast, colon, lung, and gastric cancers, and in endothelial cells from tumor associated vasculature. Therapeutic blockade of these immune checkpoint receptors is a promising strategy for neoplastic intervention by enabling anti-tumor immune responses (1-3).
4-1BB (TNFRSF9, CD137), GITR (TNFRSF18), OX40 (TNFRSF4, CD134), and CD40 ligand (CD40L, CD154, TRAP, gp39) are immune cell co-stimulatory receptors that promote effector T cell survival and activation, and enable optimal immune responses to pathogens. 4-1BB is expressed in activated CD4+ and CD8+ T cells, natural killer cells and dendritic cells. GITR is expressed constitutively at high levels on Tregs, at low levels on naive and memory T cells, and is induced upon T cell activation. Studies show GITR can also be induced on NK cells, macrophages, and DCs. GITR ligation has been shown to induce CD8+ T cell activation, cytoxicity, and memory T cell survival, and conversely inhibit Treg suppressive function while promoting effector T cell resistance to Treg suppression. OX40 is primarily expressed on activated CD4+ and CD8+ T cells, while CD40L is primarily expressed on the surface of T cells, but has also been reported in blood platelets, mast cells, basophils, NK cells, and B cells. Research studies show that agonists of these co-stimulatory receptors augment anti-tumor immunity in several cancer types. Due to the combined effects on both Treg suppression and effector cell activation, GITR represents a unique opportunity for immunotherapeutic intervention in cancer. These pathways are an important area of interest in the study of cancer, vascular diseases, and inflammatory disorders (4-7).
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