All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.
The vector of anti-HER2 chimeric antigen receptor (CAR) is constructed for the engineering of T cells to target Human HER2. The T cells are genetically modified through transduction with a lentiviral vector expressing scFv of anti-HER2 antibody linked to MyD88-CD40-FKBP and FKBP12-caspase-9 signaling domains. And the vector product was designed for the treatment of breast cancer.
CAR Construction : 4D5-8 scFv-MyD88-CD40-FKBP-CD3ζ; ∆CD19-FKBP12-caspase-9 Fig.1 Cytokine release assay. To assess antitumour activity in vitro, T cells (co-labeled with GFP) were co-cultured at various E:T ratios with the pancreatic tumour target cell line HPAC-RFP ± Rim. Two days post-seeding, culture supernatants from a duplicate plate were analyzed for IL-2 production by ELISA. Duong, M. T., Collinson-Pautz, M. R., Morschl, E., Lu, A., Szymanski, S. P., Zhang, M., ... & Bayle, J. H. (2019). Two-dimensional regulation of CAR-T cell therapy with orthogonal switches. Molecular Therapy-Oncolytics, 12, 124-137. |
CAR Construction : 4D5-8 scFv-MyD88-CD40-FKBP-CD3ζ; ∆CD19-FKBP12-caspase-9 Fig.2 Activation of the iMC switch enhances HER2 DS CAR-T cell proliferation in vitro. The co-culture containing HPAC-RFP and iRC9 or HER2 DS CAR-T cells-GFP on day 7 in the presence or absence of Rim. Duong, M. T., Collinson-Pautz, M. R., Morschl, E., Lu, A., Szymanski, S. P., Zhang, M., ... & Bayle, J. H. (2019). Two-dimensional regulation of CAR-T cell therapy with orthogonal switches. Molecular Therapy-Oncolytics, 12, 124-137. |
CAR Construction : 4D5-8 scFv-MyD88-CD40-FKBP-CD3ζ; ∆CD19-FKBP12-caspase-9 Fig.3 Tumor killing assay in vivo. iMC activation enhances HER2+ tumor killing. Duong, M. T., Collinson-Pautz, M. R., Morschl, E., Lu, A., Szymanski, S. P., Zhang, M., ... & Bayle, J. H. (2019). Two-dimensional regulation of CAR-T cell therapy with orthogonal switches. Molecular Therapy-Oncolytics, 12, 124-137. |
CAR Construction : 4D5-8 scFv-MyD88-CD40-FKBP-CD3ζ; ∆CD19-FKBP12-caspase-9 Fig.4 CAR-T proliferation assay in vivo. iMC activation enhances HER2 DS CAR-T cell proliferation. Duong, M. T., Collinson-Pautz, M. R., Morschl, E., Lu, A., Szymanski, S. P., Zhang, M., ... & Bayle, J. H. (2019). Two-dimensional regulation of CAR-T cell therapy with orthogonal switches. Molecular Therapy-Oncolytics, 12, 124-137. |
CAR Construction : Fig.5 Comparison of measured affinities of 4D5 mutated antibodies. p185HER2ECD binding affinity of mAb 4D5 variants. Carter, P., Presta, L. E. N., Gorman, C. M., Ridgway, J. B., Henner, D., Wong, W. L., ... & Shepard, H. M. (1992). Humanization of an anti-p185HER2 antibody for human cancer therapy. Proceedings of the National Academy of Sciences, 89(10), 4285-4289. |
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