pCDCAR1 HMW-MAA h(28OXζ), T(CAR-T-3-M318-2XZ)
The vector of anti-HMW-MAA chimeric antigen receptor (CAR) is constructed for the engineering of T cells to target human HMW-MAA. The T cells are genetically modified through transduction with a lentiviral vector expressing scFv of anti-HMW-MAA antibody linked to CD28 transmembrane domain/ endodomain and OX40, CD3-zeta signaling domains. And the vector product was designed for the treatment of metastatic melanoma.
Targeting Cell Type
Discription of Signaling Cassetes
CD28 (Cluster of Differentiation 28) is one of the proteins expressed on T cells that provide co-stimulatorysignals 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.
OX40, also known as CD134 or TNFRSF4 is a member of the TNFR-superfamily of receptors which is not constitutively expressed on resting naïve T cells, unlike CD28. OX40 is a secondary co-stimulatory immune checkpoint molecule, expressed after 24 to 72 hours following activation. The interaction between OX40 and its binding partner, OX40L (CD252) plays an important role in antigen-specific T-cell expansion and survival. OX40 and OX40L also regulate cytokine production from T cells and modulate cytokine receptor signaling. OX40 cosignaling in CAR improve redirected T-cell effector functions and enhance anti-tumor activity.
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.
chondroitin sulfate proteoglycan 4
CSPG4; chondroitin sulfate proteoglycan 4; NG2; MCSP; MCSPG; MSK16; HMW-MAA; MEL-CSPG; metastatic melanoma; scFv; FcεRIγ; Chimeric antigen receptor; T cell; Retrovirus; CARs; Lentivirus; chimeric T cell receptors; chimeric immunoreceptors; chimeric antigen receptors; 225.28S
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.
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