pCDCAR1 TR1 h(28CD137ζ)(CAR-MZ115)
The vector of anti-TR1 chimeric antigen receptor (CAR) is constructed for the engineering of T cells to target human TR1. The T cells are genetically modified through transduction with a retroviral vector expressing scFv of anti-TR1 antibody linked to CD28 and CD137 and CD3ζ signaling domains. And the vector product was designed for the treatment of TR-expressing tumors.
Targeting Cell Type
Discription of Signaling Cassetes
CD28 (Cluster of Differentiation 28) is one of the proteins expressed on T cells that provide co-stimulatory signals required for T cell activation and survival. CD28 is the receptor for CD80 (B7.1) and CD86 (B7.2) proteins which are expressed on antigen-presenting cells (APC). CD28 modulates the primary TCR/CD3ζ signal in a different fashion than the late costimulatory elements OX40 and 4-1BB. CD28 enhances the expression of downstream regulators that impact on T-cell proliferation, death, differentiation, and effector functions. CAR+ T cells containing the CD28 endodomain showed strikingly enhanced sustained T cell activation, growth, survival. And CD28 results in a brightly expressed, stable receptor as the transmembrane domain. Including CD28 costimulatory domains in CARs led to enhanced anti-malignancy efficacy.
CD137 is a member of the tumor necrosis factor (TNF) receptor family. Its alternative names are tumor necrosis factor receptor superfamily member 9 (TNFRSF9), 4-1BB and induced by lymphocyte activation (ILA). It is currently of interest to immunologists as a co-stimulatory immune checkpoint molecule. CD137 can be expressed by activated T cells, but to a larger extent on CD8 than on CD4 T cells. In addition, CD137 expression is found on dendritic cells, B cells, follicular dendritic cells, natural killer cells, granulocytes and cells of blood vessel walls at sites of inflammation.
CD3ζ, also known as T-cell receptor zeta, which together with T-cell receptor and CD3γ, δ , ε chain, forms the TCR-CD3 complex. ζ was expressed independently from the complex. The zeta chain plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. CD3-zeta, which contains 3 ITAMs, is the most commonly used endodomain component of CARs. It transmits an activation signal to the T cell after antigen is bound. CD3-zeta may not provide a fully competent activation signal and additional co-stimulatory signaling is needed. For example, chimeric CD28 and OX40 can be used with CD3-zeta to transmit a proliferative/survival signal, or all three can be used together.
tumor necrosis factor receptor superfamily, member 10a
TNFRSF10A; tumor necrosis factor receptor superfamily; member 10a; DR4; APO2; CD261; TRAILR1; TRAILR-1; tumor necrosis factor receptor superfamily member 10A; TRAIL-R1; TRAIL receptor 1; death receptor 4; cytotoxic TRAIL receptor; TNF-related apoptosis-inducing ligand receptor 1; tumor necrosis factor receptor superfamily member 10a variant 2; anti-DR4
For research use only. Not intended for any clinical use. No products from Creative Biolabs may be resold, modified for resale or used to manufacture commercial products without prior written approval from Creative Biolabs.