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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)
CAR Construction : SS1 scfv-41BB-CD3ζ 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. |
CAR Construction : SS1 scfv-41BB-CD3ζ 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. |
CAR Construction : SS1 scfv-41BB-CD3ζ 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. |
CAR Construction : SS1 scfv-41BB-CD3ζ 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. |
CAR Construction : SS1 scfv-41BB-CD3ζ 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. |
CAR Construction : SS1 scfv-41BB-CD3ζ 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 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. |
CAR Construction : SS1 scfv-41BB-CD3ζ 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. |
CAR Construction : SS1 scfv-41BB-CD3ζ 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. |
CAR Construction : SS1 scfv-41BB-CD3ζ 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 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. |
CAR Construction : SS1 scfv-41BB-CD3ζ 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. |
CAR Construction : SS1 scfv-41BB-CD3ζ 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. |
CAR Construction : SS1 scfv-41BB-CD3ζ 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. |
CAR Construction : SS1 scfv-41BB-CD3ζ 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. |
CAR Construction : SS1 scfv-41BB-CD3ζ 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. |
CAR Construction : SS1 scfv-41BB-CD3ζ 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. |
CAR Construction : SS1 scfv-41BB-CD3ζ 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. |
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