pCDCAR1 ErbB2 h(28FcεRIγ), T(CAR-T-2-L337-2G)
The vector of anti-ErbB2 chimeric antigen receptor (CAR) is constructed for the engineering of T cells to target human ErbB2. The T cells are genetically modified through transduction with a lentiviral vector expressing scFv of anti-ErbB2 antibody linked to a CD28 transmembrane domain/ endodomain and FcεRIγ signaling domains. And the vector product was designed as a medicament, in particular in the treatment of cancer and in adoptive, target-cell specific immunotherapy.
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.
The high-affinity IgE receptor, also known as FcεRI, or Fc epsilon RI, is the high-affinity receptor for the Fc region of immunoglobulin E (IgE). FcεRI is a key molecule involved in allergic reactions. It is a tetramer composed of 1alpha, 1 beta, and 2 gamma chains. The gamma chains are also subunits of other Fc receptors. The scFv-based CARs engineered to contain a signaling domain from FcεRIγ have been shown to deliver a potent signal for T cell activation and function.
erb-b2 receptor tyrosine kinase 2
ERBB2; erb-b2 receptor tyrosine kinase 2; NEU; NGL; HER2; TKR1; CD340; HER-2; MLN 19; HER-2/neu; receptor tyrosine-protein kinase erbB-2; herstatin; p185erbB2; proto-oncogene Neu; c-erb B2/neu protein; proto-oncogene c-ErbB-2; metastatic lymph node gene 19 protein; human epidermal growth factor receptor 2; neuro/glioblastoma derived oncogene homolog; tyrosine kinase-type cell surface receptor HER2; neuroblastoma/glioblastoma derived oncogene homolog; v-erb-b2 avian erythroblastic leukemia viral oncoprotein 2; v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2; v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog; CD28; Chimeric antigen receptor; T cell; Retrovirus; CARs; Lentivirus; chimeric T cell receptors; chimeric immunoreceptors; chimeric antigen receptors; scFv; OTI5C4
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