pCDCAR3 FOLH1×CD19 h(ζ/28BB)(CAR-LC362)
The T cells are genetically modified through transduction with one retroviral vector expressing anti-PSMA antibody scFv linked to CD28 and 4-1BB signaling domain, and a second vector expressing anti-CD19 antibody scFv linked to CD3ζ signaling domain. The dual CAR-modified T cell activation requires co-expression of both PSMA and CD19 on tumor cells.The product was designed for the treatment of prostate cancer.
Targeting Cell Type
scFv (PSMA)-CD28-41BB/scFv (CD19)-CD3ζ
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 (also known as 4-1BB) is a surface co-stimulatory glycoprotein originally described as present on activated T lymphocytes, which belongs to the tumor necrosis factor (TNF) receptor superfamily. It is expressed mainly on activated CD4+ and CD8+ T cells, and binds to a high-affinity ligand (4-1BBL) expressed on several antigen-presenting cells such as macrophages and activated B cells. On the basis of preclinical observation, this molecule can promote the persistence of antigen-specific and antigen-nonspecific chimeric antigen receptor T-cells to significantly increases antitumor 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.
folate hydrolase (prostate-specific membrane antigen) 1
FOLH1; folate hydrolase (prostate-specific membrane antigen) 1; PSM; FGCP; FOLH; GCP2; PSMA; mGCP; GCPII; NAALAD1; NAALAdase; glutamate carboxypeptidase 2; NAALADase I; glutamate carboxylase II; glutamate carboxypeptidase II; membrane glutamate carboxypeptidase; cell growth-inhibiting gene 27 protein; folylpoly-gamma-glutamate carboxypeptidase; prostate specific membrane antigen variant F; pteroylpoly-gamma-glutamate carboxypeptidase; N-acetylated alpha-linked acidic dipeptidase 1; N-acetylated-alpha-linked acidic dipeptidase I;
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.