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pCDCAR1 mesothelin h(28BBζ), T (CAR-T-3-M321-2BZ)

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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 CD137 (4-1BB), 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-CD28-41BB-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.
    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
  • 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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