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Anti-CD38 (028) h(41BB-CD3ζ) CAR, pCDCAR1 (CAR-MZ160)


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

The vector of anti-CD38 chimeric antigen receptor (CAR) is constructed for the engineering of T cells to target human CD38. The T cells are genetically modified through transduction with a retroviral vector expressing scFv of anti-CD38 antibody linked to 41BB and CD3ζ signaling domains. And the vector product was designed for the treatment of Multiple myeloma.

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Details

  • Target
  • CD38
  • Targeting Cell Type
  • T cell
  • Targeting Diseases
  • Multiple myeloma
  • Generation
  • Second
  • Vector Name
  • pCDCAR1
  • Vector Length
  • ~8kb
  • Vector Type
  • Retroviral
  • Receptor Construction
  • scFv-41BB-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 antigen-nonspecific 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
  • 028
  • Host
  • Human
  • Target Species
  • Human
  • Gene Name
  • CD38
  • Synonyms
  • CD38;CD38; CD38 Molecule; CD38 Molecule; ADP-Ribosyl Cyclase 1; 2-Phospho-Cyclic-ADP-Ribose Transferase; Cyclic ADP-Ribose Hydrolase 1; 2-Phospho-ADP-Ribosyl Cyclase; NAD(+) Nucleosidase; CD38 Antigen (P45); ADPRC 1; 2-Phospho-ADP-Ribosyl Cyclase/2-Phospho-Cyclic-ADP-Ribose Transferase; Ecto-Nicotinamide Adenine Dinucleotide Glycohydrolase;

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  • Published Data
Complete CAR data FCM

Fig.1 Efficacy of CD38-CART cells at lysing MM cell lines.

CAR Construction : 028-41BB-CD3ζ Latest CAR Construction

Fig.1 Efficacy of CD38-CART cells at lysing MM cell lines.

In 24 h cytotoxicity assays, three different types of CD38-CART cells were tested against two MM cell lines with different CD38 expression levels: (Upper) U266, a CD38− cell line, (Bottom) UM9, a CD38+ cell line.

Drent, E., Groen, R. W., Noort, W. A., Themeli, M., van Bueren, J. J. L., Parren, P. W., ... & Mutis, T. (2016). Pre-clinical evaluation of CD38 chimeric antigen receptor engineered T cells for the treatment of multiple myeloma. Haematologica, 101(5), 616.

Complete CAR data FuncS

Fig.2 Cytokine release assay.

CAR Construction : 028-41BB-CD3ζ Latest CAR Construction

Fig.2 Cytokine release assay.

24 hr after co-incubation with the CD38+ target cell line UM9 or CD38 target U266, E:T ratio 1:1, cytokine secretion by mock or CD38-CAR028, A1, A4, B1, or B3 T cells was measured with a flow-cytometry-based assay in the cell-free supernatants.

Drent, E., Themeli, M., Poels, R., de Jong-Korlaar, R., Yuan, H., de Bruijn, J., ... & Mutis, T. (2017). A rational strategy for reducing on-target off-tumor effects of CD38-chimeric antigen receptors by affinity optimization. Molecular therapy, 25(8), 1946-1958.

Complete CAR data FCM

Fig.3 CART cell phenotyping assay.

CAR Construction : 028-41BB-CD3ζ Latest CAR Construction

Fig.3 CART cell phenotyping assay.

Phenotypic profile of each CD38-CAR T cell type was determined before (week 0) and after (week 1) expansion with markers CD45RA and CD62L. Percentage of total cells is depicted for naive (CD45RA+/CD62L+), central memory (CM) (CD45RA/CD62L+), effector memory (EM) (CD45RA/CD62L), and effector(CD45RA+/CD62L).

Drent, E., Themeli, M., Poels, R., de Jong-Korlaar, R., Yuan, H., de Bruijn, J., ... & Mutis, T. (2017). A rational strategy for reducing on-target off-tumor effects of CD38-chimeric antigen receptors by affinity optimization. Molecular therapy, 25(8), 1946-1958.

Complete CAR data BI

Fig.4 In vivo efficacy of CD38-CAR-T cells.

CAR Construction : 028-41BB-CD3ζ Latest CAR Construction

Fig.4 In vivo efficacy of CD38-CAR-T cells.

Mice were i.v. injected with 10* 10^6 cells of tumor cell line UM9 and treated 1 week after with i.v. injections of 5 * 10^6 mock, high-affinity CD38-CAR028, or low-affinity CD38-CARA4 T cells.

Drent, E., Themeli, M., Poels, R., de Jong-Korlaar, R., Yuan, H., de Bruijn, J., ... & Mutis, T. (2017). A rational strategy for reducing on-target off-tumor effects of CD38-chimeric antigen receptors by affinity optimization. Molecular therapy, 25(8), 1946-1958.

Complete CAR data BI

Fig.5 The lytic capacity of CD38-CART cells.

CAR Construction : 028-41BB-CD3ζ, 028-CD28-CD3ζ, 028-CD28-CD3ζ-41BBL Latest CAR Construction

Fig.5 The lytic capacity of CD38-CART cells.

The series of high and low affinity CAR T cells were incubated with Firefly-Luciferase-transduced human MM cell line UM9.

Drent, E., Poels, R., Ruiter, R., van de Donk, N. W., Zweegman, S., Yuan, H., ... & Themeli, M. (2019). Combined CD28 and 4-1BB Costimulation Potentiates Affinity-tuned Chimeric Antigen Receptor–engineered T CellsDual Costimulation Empowers Very Low–affinity CAR-T Cells. Clinical Cancer Research, 25(13), 4014-4025.

Complete CAR data FCM

Fig.6 Cytokine release assay.

CAR Construction : 028-41BB-CD3ζ, 028-CD28-CD3ζ, 028-CD28-CD3ζ-41BBL Latest CAR Construction

Fig.6 Cytokine release assay.

24 hours after co-incubation with UM9 (E:T ratio 1:1), cell supernatants were harvested to measure cytokine secretion with a flow cytometry-based assay. Graph shows the secretion of IFN-γ, TNF and IL-2.

Drent, E., Poels, R., Ruiter, R., van de Donk, N. W., Zweegman, S., Yuan, H., ... & Themeli, M. (2019). Combined CD28 and 4-1BB Costimulation Potentiates Affinity-tuned Chimeric Antigen Receptor–engineered T CellsDual Costimulation Empowers Very Low–affinity CAR-T Cells. Clinical Cancer Research, 25(13), 4014-4025.

Complete CAR data FCM

Fig.7 Exhaustion of CD38-CAR T cells.

CAR Construction : 028-41BB-CD3ζ, 028-CD28-CD3ζ, 028-CD28-CD3ζ-41BBL Latest CAR Construction

Fig.7 Exhaustion of CD38-CAR T cells.

Pie charts illustrating the % of cells expressing either 0, 1 (PD-1+, Lag3+ or TIM3+), 2 (PD-1+/Lag3+ or PD-1+/TIM3+ or Lag3+/TIM3+) or 3 (PD-1+, Lag3+ and TIM3+) exhaustion markers gated on live CD3+CAR+ cells.

Drent, E., Poels, R., Ruiter, R., van de Donk, N. W., Zweegman, S., Yuan, H., ... & Themeli, M. (2019). Combined CD28 and 4-1BB Costimulation Potentiates Affinity-tuned Chimeric Antigen Receptor–engineered T CellsDual Costimulation Empowers Very Low–affinity CAR-T Cells. Clinical Cancer Research, 25(13), 4014-4025.

CAR scFv data SPR

Fig.8 Binding affinity of anti-CD38 scFv antibodies.

CAR Construction : Latest CAR Construction

Fig.8 Binding affinity of anti-CD38 scFv antibodies.

Binding kinetics of anti-CD38 028 scFv antibodies against purified hCD38-ECD were investigated by biolayer interferometry.

Ma, P., Ren, P., Zhang, C., Tang, J., Yu, Z., Zhu, X., ... & Lerner, R. A. (2021). Avidity‐Based Selection of Tissue‐Specific CAR‐T Cells from a Combinatorial Cellular Library of CARs. Advanced Science, 8(6), 2003091.

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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