All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.
The vector of anti-HIV-1 chimeric antigen receptor (CAR) is constructed for the engineering of T cells to target HIV-1. The T cells are genetically modified through transduction with a lentiviral vector expressing scFv of anti-HIV-1 antibody linked to 41BB and CD3ζ signaling domains. And the vector product was designed for the treatment of HIV-1 infection.
CAR Construction : PGT128-CD3ζ Fig.1 Specific killing assay. Specific lysis of Cr51 labeled K562 target cells expressing HIV-1 YU2 GP160. Leibman, R. S., Richardson, M. W., Ellebrecht, C. T., Maldini, C. R., Glover, J. A., Secreto, A. J., ... & Riley, J. L. (2017). Supraphysiologic control over HIV-1 replication mediated by CD8 T cells expressing a re-engineered CD4-based chimeric antigen receptor. PLoS pathogens, 13(10), e1006613. |
CAR Construction : PGT128-41BB-CD3ζ Fig.2 Proliferation mediated by novel CAR interactions with HIV-1-infected target cells. Primary CD8+ T lymphocytes transduced with CARs were enriched to>90% purity and labeled with CellTrace Violet and then cocultured with irradiated HIV-1 NL4-3-infected T2 cells. Ali, A., Kitchen, S. G., Chen, I. S., Ng, H. L., Zack, J. A., & Yang, O. O. (2016). HIV-1-specific chimeric antigen receptors based on broadly neutralizing antibodies. Journal of virology, 90(15), 6999-7006. |
CAR Construction : PGT128-41BB-CD3ζ Fig.3 Specific killing of HIV-1-infected target cells mediated by novel CARs. CAR-transduced primary CD8+ T lymphocytes were cocultured with HIV-1-infected T2 cells in standard 4-h chromium release assays to assess killing mediated by the CARs. Ali, A., Kitchen, S. G., Chen, I. S., Ng, H. L., Zack, J. A., & Yang, O. O. (2016). HIV-1-specific chimeric antigen receptors based on broadly neutralizing antibodies. Journal of virology, 90(15), 6999-7006. |
CAR Construction : PGT128-41BB-CD3ζ Fig.4 Relative cytotoxicity. Comparison of the specific cytotoxicity induced by anti-HIV-1 CAR. Kranz, E., Chan, J., Hashimoto, M., Kanazawa, T., Wang, H., & Kamata, M. (2020). Membrane-proximal external region is a superior target for mediating effector activity of HIV-1 specific chimeric antigen receptor modified T cells. bioRxiv. |
CAR Construction : PGT128-41BB-CD3ζ Fig.5 TNF-α, IL-2 and IFN-γ production in co-cultures. Production of three different cytokines (IFN-γ, IL-2, and TNF-α) in CAR-modified CD4 and CD8 T cells was monitored by flow cytometry. Kranz, E., Chan, J., Hashimoto, M., Kanazawa, T., Wang, H., & Kamata, M. (2020). Membrane-proximal external region is a superior target for mediating effector activity of HIV-1 specific chimeric antigen receptor modified T cells. bioRxiv. |
CAR Construction : PGT126-41BB-CD3ζ Fig.6 Efficiencies of novel CAR-transduced primary CD8+ T cells against a panel of HIV-1 isolates CAR-transduced primary CD8+ T cells were tested against a panel of 4 subtype B viruses and one subtype C virus (TZA246) to determine the percent efficiency of log suppression Ali, A., Kitchen, S. G., Chen, I. S., Ng, H. L., Zack, J. A., & Yang, O. O. (2016). HIV-1-specific chimeric antigen receptors based on broadly neutralizing antibodies. Journal of virology, 90(15), 6999-7006. |
CAR Construction : Fig.7 Antibody binding affinity measurements. The sensorgrams show the binding (RU) of the listed IgGs to the BG505 SOSIP.664 trimer, gp120-gp41ECTO protomer (gp140), and monomeric gp120 over time (s) on the x axis. Yasmeen, A., Ringe, R., Derking, R., Cupo, A., Julien, J. P., Burton, D. R., ... & Klasse, P. J. (2014). Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. Retrovirology, 11(1), 1-17. |
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