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pCDCAR1 DR5 h(BBζ) (CAR-ZP10160)


All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.

The vector of anti-DR5 chimeric antigen receptor (CAR) is constructed for the engineering of T cells to target Human DR5. The T cells are genetically modified through transduction with a lentiviral vector expressing scFv of anti-DR5 antibody linked to 4-1BB and CD3ζ signaling domains. And the vector product was designed for the treatment of Breast cancer.

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Details

  • Target
  • DR5
  • Targeting Cell Type
  • T cell
  • Targeting Diseases
  • Breast cancer
  • Generation
  • Second
  • Vector Name
  • pCDCAR1
  • Vector Length
  • ~8kb
  • Vector Type
  • Lentiviral vector
  • Receptor Construction
  • scFv-4-1BB-CD3ζ
  • Discription of Signaling Cassetes
  • 41BB
    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 antigennonspecific chimeric antigen receptor T-cells to significantly increases antitumor activity.
    CD3ζ
    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.

Target

  • Clone
  • KMTR2
  • Host
  • Human
  • Target Species
  • Human
  • Gene Name
  • TNF receptor superfamily member 10b
  • Synonyms
  • DR5; CD262; KILLER; TRICK2; TRICKB; ZTNFR9; TRAILR2; TRICK2A; TRICK2B; TRAIL-R2; KILLER/DR5

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  • Published Data
CAR scFv data FCM

Fig.1 Flow cytometry results of KMTR2 and its mutant (LkN53R) to TRAIL-R2. Antibody concentrations are 100ng/mL (upper) and 1000ng/mL (lower).

CAR Construction : Latest CAR Construction

Fig.1 Flow cytometry results of KMTR2 and its mutant (LkN53R) to TRAIL-R2. Antibody concentrations are 100ng/mL (upper) and 1000ng/mL (lower).

X-axis indicates R-phycoerythrin (RPE) fuorescence signal intensity.

Tamada, T., Shinmi, D., Ikeda, M., Yonezawa, Y., Kataoka, S., Kuroki, R., ... & Motoki, K. (2015). TRAIL-R2 superoligomerization induced by human monoclonal agonistic antibody KMTR2. Scientific Reports, 5(1), 1-12.

CAR scFv data ELISA

Fig.2 Binding activities of KMTR2 and its mutant (LkN53R) to TRAIL-R2.

CAR Construction : Latest CAR Construction

Fig.2 Binding activities of KMTR2 and its mutant (LkN53R) to TRAIL-R2.

Data for KMTR2 and the LkN53R mutant are shown as solid and dashed lines, respectively.

Tamada, T., Shinmi, D., Ikeda, M., Yonezawa, Y., Kataoka, S., Kuroki, R., ... & Motoki, K. (2015). TRAIL-R2 superoligomerization induced by human monoclonal agonistic antibody KMTR2. Scientific Reports, 5(1), 1-12.

CAR scFv data FCM

Fig.3 ApoEVs isolated from DR5-WT OVCAR-3cells (KMTR2treated) were added on to DR5-KO (MDA-MB-231) cells for indicated times (24–96h) to analyze PD-L1transfer kinetics from ApoEV.

CAR Construction : Latest CAR Construction

Fig.3 ApoEVs isolated from DR5-WT OVCAR-3cells (KMTR2treated) were added on to DR5-KO (MDA-MB-231) cells for indicated times (24–96h) to analyze PD-L1transfer kinetics from ApoEV.

All measurements were performed in triplicate.

Mondal, T., Shivange, G. N., Tihagam, R. G., Lyerly, E., Battista, M., Talwar, D., ... & Tushir‐Singh, J. (2021). Unexpected PD‐L1 immune evasion mechanism in TNBC, ovarian, and other solid tumors by DR5 agonist antibodies. EMBO Molecular Medicine, 13(3), e12716.

CAR scFv data FCM

Fig.4 PD-L1 surface histogram from DR5-KO cells after treatment (24h) with ApoEVs isolated from DR5-sensitive cells after either Lexa or KMTR2 treatment.

CAR Construction : Latest CAR Construction

Fig.4 PD-L1 surface histogram from DR5-KO cells after treatment (24h) with ApoEVs isolated from DR5-sensitive cells after either Lexa or KMTR2 treatment.

All measurements were performed in triplicate.

Mondal, T., Shivange, G. N., Tihagam, R. G., Lyerly, E., Battista, M., Talwar, D., ... & Tushir‐Singh, J. (2021). Unexpected PD‐L1 immune evasion mechanism in TNBC, ovarian, and other solid tumors by DR5 agonist antibodies. EMBO Molecular Medicine, 13(3), e12716.

More Published Data More Published Data

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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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