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The vector of anti-CD4 chimeric antigen receptor (CAR) is constructed for the engineering of T cells to target human CD4. The T cells are genetically modified through transduction with a lentiviral vector expressing scFv of anti-CD4 antibody linked to CD28, 4-1BB (CD137) and CD3ζ signaling domains. And the vector product was designed for the treatment of non-Hodgkin's lymphomas.
CAR Construction : hu5A8-CD28-41BB-CD3ζ Fig.1 The immunophenotype of CD4CAR T cells. The immunophenotype of CD4CAR T cells was evaluated at the end of each culture. Pinz, K., Liu, H., Golightly, M., Jares, A., Lan, F., Zieve, G. W., ... & Ma, Y. (2016). Preclinical targeting of human T-cell malignancies using CD4-specific chimeric antigen receptor (CAR)-engineered T cells. Leukemia, 30(3), 701-707. |
CAR Construction : hu5A8-CD28-41BB-CD3ζ Fig.2 CD4CAR T cells derived from PBMCs specifically kill CD4-expressing the tumor cell line. KARPAS 299 cells incubated with CD4CAR T cells overnight were eliminated at a rate of 38%, 62%, and 85%, at E:T ratios of 2:1, 5:1, and 10:1 Pinz, K., Liu, H., Golightly, M., Jares, A., Lan, F., Zieve, G. W., ... & Ma, Y. (2016). Preclinical targeting of human T-cell malignancies using CD4-specific chimeric antigen receptor (CAR)-engineered T cells. Leukemia, 30(3), 701-707. |
CAR Construction : hu5A8-CD28-41BB-CD3ζ Fig.3 The anti-tumor activity of CD4CAR T cells in vivo. Treatment with CD4CAR T cells significantly prolonged the survival of mice bearing KARPAS 299 lymphoma as compared to treatment with the GFP-transduced control T cells. Pinz, K., Liu, H., Golightly, M., Jares, A., Lan, F., Zieve, G. W., ... & Ma, Y. (2016). Preclinical targeting of human T-cell malignancies using CD4-specific chimeric antigen receptor (CAR)-engineered T cells. Leukemia, 30(3), 701-707. |
CAR Construction : hu5A8-CD28-41BB-CD3ζ Fig.4 AAV-CD4CAR induces antitumor activity in vitro. 48 hours after co-culture with AAV-CD4CAR T cells, MT2, and Jurkat cells were effectively lysed in a dose-dependent manner. However, neither the CD4- cell line (H929) nor the MT2 cells treated with a CD20-CAR were lysed. Nawaz, W., Huang, B., Xu, S., Li, Y., Zhu, L., Yiqiao, H., ... & Wu, X. (2021). AAV-mediated in vivo CAR gene therapy for targeting human T-cell leukemia. Blood cancer journal, 11(6), 1-12. |
CAR Construction : hu5A8-CD28-41BB-CD3ζ Fig.5 Cytokine production in an ATL NCG-HuPBL mouse model. Graphical representation of different cytokines detected in the plasma of tumor-bearing ATL NCG-HuPBL mice. Nawaz, W., Huang, B., Xu, S., Li, Y., Zhu, L., Yiqiao, H., ... & Wu, X. (2021). AAV-mediated in vivo CAR gene therapy for targeting human T-cell leukemia. Blood cancer journal, 11(6), 1-12. |
CAR Construction : hu5A8-CD28-41BB-CD3ζ Fig.6 In vivo-generated AAV-CD4CAR T cells mediated antitumor activity. In vivo imaging of luciferase-expressing MT2 ATL cells injected into NCG-HuPBL mice after AAV or PBS (untreated) injection. Nawaz, W., Huang, B., Xu, S., Li, Y., Zhu, L., Yiqiao, H., ... & Wu, X. (2021). AAV-mediated in vivo CAR gene therapy for targeting human T-cell leukemia. Blood cancer journal, 11(6), 1-12. |
CAR Construction : hu5A8-CD28-41BB-CD3ζ Fig.7 Anti-leukemic effects of CD4CAR NK cells in vivo. NSG mice bearing luciferase-expressing KARPAS-299 cells were treated with CD4CAR NK cells or vector control NK cells. Pinz, K. G., Yakaboski, E., Jares, A., Liu, H., Firor, A. E., Chen, K. H., ... & Ma, Y. (2017). Targeting T-cell malignancies using anti-CD4 CAR NK-92 cells. Oncotarget, 8(68), 112783. |
CAR Construction : Fig.8 Affinity determination of ibalizumab. Binding affinity of ibalizumab to hCD4 as assessed in a Biacore assay. Song, R., Franco, D., Kao, C. Y., Yu, F., Huang, Y., & Ho, D. D. (2010). Epitope mapping of ibalizumab, a humanized anti-CD4 monoclonal antibody with anti-HIV-1 activity in infected patients. Journal of virology, 84(14), 6935-6942. |
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