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pCDCAR1 mesothelin h(28OXζ), T (CAR-T-3-M321-2XZ)


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

The vector of anti-mesothelin chimeric antigen receptor (CAR) is constructed for the engineering of T cells to target human mesothelin. The T cells are genetically modified through transduction with a lentiviral vector expressing scFv of anti-mesothelin antibody linked to CD28 transmembrane domain/ endodomain and OX40, CD3-zeta signaling domains. And the vector product was designed for the treatment of pancreatic cancer, ovarian cancer, lung cancer, malignant pleural mesothelioma tumors (MPM tumors)

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Details

  • Target
  • mesothelin
  • Targeting Cell Type
  • T cell
  • Targeting Diseases
  • Pancreatic cancer; ovarian cancer; lung cancer; malignant pleural mesothelioma tumors(MPM tumors)
  • Generation
  • Third
  • Vector Name
  • pCDCAR1
  • Vector Length
  • 8kb
  • Vector Type
  • Lentiviral
  • Receptor Construction
  • scFv-CD28-OX40-CD3ζ
  • Discription of Signaling Cassetes
  • CD28
    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
    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
    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
  • SS1
  • Host
  • Mouse
  • Target Species
  • Human
  • Gene Name
  • mesothelin
  • Synonyms
  • Mesothelin;MSLN; mesothelin; MPF; SMRP;

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  • Published Data
Complete CAR data Funcs

Fig.1 In vitro anti-tumor activity of hYP218 and SS1 CAR T cells.

CAR Construction : SS1 scfv-41BB-CD3ζ Latest CAR Construction

Fig.1 In vitro anti-tumor activity of hYP218 and SS1 CAR T cells.

Killing of mesothelin-expressing OVCAR-8 cells upon co-culture with untransduced, SS1 CAR or hYP218 CAR T cells at different Effector to Target ratios (E:T).

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.

Complete CAR data Funcs

Fig.2 Percent killing of different mesothelin-expressing tumor cells upon co-culture with SS1 CAR or hYP218 CAR T cells at E:T of 3.

CAR Construction : SS1 scfv-41BB-CD3ζ Latest CAR Construction

Fig.2 Percent killing of different mesothelin-expressing tumor cells upon co-culture with SS1 CAR or hYP218 CAR T cells at E:T of 3.

Mesothelin-negative cell lines A431, KLM1 MSLN k/o and H1703 were used as negative controls. hYP218-CAR (Red), SS1-CAR (Grey).

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.

Complete CAR data Funcs

Fig.3 Release of cytokines IFN-γ upon co-culture of tumor cells with hYP218 CAR T cells.

CAR Construction : SS1 scfv-41BB-CD3ζ Latest CAR Construction

Fig.3 Release of cytokines IFN-γ upon co-culture of tumor cells with hYP218 CAR T cells.

hYP218-CAR (Red), SS1-CAR (Grey).

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.

Complete CAR data Funcs

Fig.4 Release of cytokines IL-2 upon co-culture of tumor cells with hYP218 CAR T cells.

CAR Construction : SS1 scfv-41BB-CD3ζ Latest CAR Construction

Fig.4 Release of cytokines IL-2 upon co-culture of tumor cells with hYP218 CAR T cells.

hYP218-CAR (Red), SS1-CAR (Grey).

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.

Complete CAR data Funcs

Fig.5 Release of cytokines TNF-α upon co-culture of tumor cells with hYP218 CAR T cells.

CAR Construction : SS1 scfv-41BB-CD3ζ Latest CAR Construction

Fig.5 Release of cytokines TNF-α upon co-culture of tumor cells with hYP218 CAR T cells.

hYP218-CAR (Red), SS1-CAR (Grey).

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.

Complete CAR data Funcs

Fig.6 In vivo anti-tumor efficacy of hYP218 and SS1 CAR T cells using ovarian cancer mesothelin-expressing tumor models.

CAR Construction : SS1 scfv-41BB-CD3ζ Latest CAR Construction

Fig.6 In vivo anti-tumor efficacy of hYP218 and SS1 CAR T cells using ovarian cancer mesothelin-expressing tumor models.

Bioluminescence imaging (BLI) of OVCAR-8 tumor growth in NSG mice treated with CAR T cells, red arrow indicates CAR T cell infusion on day 14 after tumor
implantation.

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.

Complete CAR data Funcs

Fig.7 In vivo anti-tumor efficacy of hYP218 and SS1 CAR T cells using ovarian cancer mesothelin-expressing tumor models.

CAR Construction : SS1 scfv-41BB-CD3ζ Latest CAR Construction

Fig.7 In vivo anti-tumor efficacy of hYP218 and SS1 CAR T cells using ovarian cancer mesothelin-expressing tumor models.

Kinetics of OVCAR-8 tumor growth.

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.

Complete CAR data Funcs

Fig.8 In vivo anti-tumor efficacy of hYP218 and SS1 CAR T cells using ovarian cancer mesothelin-expressing tumor models.

CAR Construction : SS1 scfv-41BB-CD3ζ Latest CAR Construction

Fig.8 In vivo anti-tumor efficacy of hYP218 and SS1 CAR T cells using ovarian cancer mesothelin-expressing tumor models.

Overall survival of OVCAR-8 tumor implanted mice in different treatment groups.

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.

Complete CAR data Funcs

Fig.9 In vivo anti-tumor efficacy of hYP218 and SS1 CAR T cells using pancreatic cancer mesothelin-expressing tumor models.

CAR Construction : SS1 scfv-41BB-CD3ζ Latest CAR Construction

Fig.9 In vivo anti-tumor efficacy of hYP218 and SS1 CAR T cells using pancreatic cancer mesothelin-expressing tumor models.

Bioluminescence imaging (BLI) of KLM-1 tumor growth in NSG mice treated with CAR T cells, red arrow indicates CAR T cell infusion on day 14 after tumor
implantation.

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.

Complete CAR data Funcs

Fig.10 In vivo anti-tumor efficacy of hYP218 and SS1 CAR T cells using pancreatic cancer mesothelin-expressing tumor models.

CAR Construction : SS1 scfv-41BB-CD3ζ Latest CAR Construction

Fig.10 In vivo anti-tumor efficacy of hYP218 and SS1 CAR T cells using pancreatic cancer mesothelin-expressing tumor models.

Kinetics of KLM-1 tumor growth.

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.

Complete CAR data Funcs

Fig.11 In vivo anti-tumor efficacy of hYP218 and SS1 CAR T cells using pancreatic cancer mesothelin-expressing tumor models.

CAR Construction : SS1 scfv-41BB-CD3ζ Latest CAR Construction

Fig.11 In vivo anti-tumor efficacy of hYP218 and SS1 CAR T cells using pancreatic cancer mesothelin-expressing tumor models.

Overall survival of KLM-1 tumor implanted mice in different treatment groups.

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.

Complete CAR data Funcs

Fig.12 Anti-tumor efficacy of hYP218 and SS1 CAR T cells using a mesothelioma patient derived cell line xenograft model.

CAR Construction : SS1 scfv-41BB-CD3ζ Latest CAR Construction

Fig.12 Anti-tumor efficacy of hYP218 and SS1 CAR T cells using a mesothelioma patient derived cell line xenograft model.

Killing of mesothelioma patient-derived NCI-Meso63 tumor cells upon co-culture with autologous untransduced, SS1 CAR or hYP218 CAR T cells derived from the PBMCs from the same patient at different E:T ratios.

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.

Complete CAR data Funcs

Fig.13 Anti-tumor efficacy of hYP218 and SS1 CAR T cells using a mesothelioma patient derived cell line xenograft model.

CAR Construction : SS1 scfv-41BB-CD3ζ Latest CAR Construction

Fig.13 Anti-tumor efficacy of hYP218 and SS1 CAR T cells using a mesothelioma patient derived cell line xenograft model.

Kinetics of NCI-Meso63 mesothelioma tumor growth in mice implanted with subcutaneous NCI-Meso63 cells. CAR T cells were infused on day 14 after tumor implantation.

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.

Complete CAR data Funcs

Fig.14 In vivo tumor infiltration and persistence of CAR T cells in the blood and tumors of KLM-1 tumor bearing mice.

CAR Construction : SS1 scfv-41BB-CD3ζ Latest CAR Construction

Fig.14 In vivo tumor infiltration and persistence of CAR T cells in the blood and tumors of KLM-1 tumor bearing mice.

Representative FCM analysis (n = 1 mouse) detecting the presence of hCD45+hCD3+ double-positive human T cells in the blood (left panel) and tumors (central panel) of NSG mice implanted with KLM-1 tumors, on days 2 and day 7 after CAR T cell infusion.

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.

Complete CAR data Funcs

Fig.15 In vivo tumor infiltration and persistence of CAR T cells in the blood and tumors of KLM-1 tumor bearing mice.

CAR Construction : SS1 scfv-41BB-CD3ζ Latest CAR Construction

Fig.15 In vivo tumor infiltration and persistence of CAR T cells in the blood and tumors of KLM-1 tumor bearing mice.

Change in the number of hCD45+ hCD3+ human T cells in 100 mcL blood from day 2 to day 7 after CAR T cell infusion (n=3). hYP218-CAR (Red), SS1-CAR (Grey).

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.

Complete CAR data Funcs

Fig.16 In vivo tumor infiltration and persistence of CAR T cells in the blood and tumors of KLM-1 tumor bearing mice.

CAR Construction : SS1 scfv-41BB-CD3ζ Latest CAR Construction

Fig.16 In vivo tumor infiltration and persistence of CAR T cells in the blood and tumors of KLM-1 tumor bearing mice.

Change in the percentage of tumor infiltrating hCD45+hCD3+ human T cells from day 2 to day 7 after CAR T cell infusion (n=3).

Tomar, S., Zhang, J., Khanal, M., Hong, J., Venugopalan, A., Jiang, Q., ... & Hassan, R. (2022). Development of highly effective anti-mesothelin Hyp218 chimeric antigen receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Molecular cancer therapeutics, 21(7), 1195.

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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