Anti-DR5 (Drozitumab) h(CD28-CD3ζ) CAR, pSBCAR1 (CAR-SB-LX0199)

CAR Construction :

Fig.2 The growth of three different established patient-derived xenografts is inhibited by treatment with drozitumab.

SCID mice implanted with tumors.

Eng, J. W. L., Mace, T. A., Sharma, R., Twum, D. Y., Peng, P., Gibbs, J. F., ... & Hylander, B. L. (2016). Pancreatic cancer stem cells in patient pancreatic xenografts are sensitive to drozitumab, an agonistic antibody against DR5. Journal for immunotherapy of cancer, 4, 1-11.

CAR Construction :

Fig.3 Cancer stems cells undergo apoptosis following treatment with drozitumab.

Dissociated tumor cells from 11424, 14244 and 12424 treated in vitro with 10 μg/ml of drozitumab antibody for 1 h and incubated for 7 h with 10 μg/ml of anti-human Fc IgG antibody.

Eng, J. W. L., Mace, T. A., Sharma, R., Twum, D. Y., Peng, P., Gibbs, J. F., ... & Hylander, B. L. (2016). Pancreatic cancer stem cells in patient pancreatic xenografts are sensitive to drozitumab, an agonistic antibody against DR5. Journal for immunotherapy of cancer, 4, 1-11.

CAR Construction :

Fig.4 Mice were treated with 200 μg drozitumab and tumors were resected, disaggregated and percentage of cleaved caspase-3 in CSCs vs. bulk tumor cells analyzed by flow cytometry.

Treatment of tumor bearing mice in vivo with drozitumab induces apoptosis primarily in triple positive cells.

Eng, J. W. L., Mace, T. A., Sharma, R., Twum, D. Y., Peng, P., Gibbs, J. F., ... & Hylander, B. L. (2016). Pancreatic cancer stem cells in patient pancreatic xenografts are sensitive to drozitumab, an agonistic antibody against DR5. Journal for immunotherapy of cancer, 4, 1-11.

CAR Construction :

Fig.5 Drozitumab treatment depletes DR5+ cells in vitro.

Experiment performed twice in triplicate.

Eng, J. W. L., Mace, T. A., Sharma, R., Twum, D. Y., Peng, P., Gibbs, J. F., ... & Hylander, B. L. (2016). Pancreatic cancer stem cells in patient pancreatic xenografts are sensitive to drozitumab, an agonistic antibody against DR5. Journal for immunotherapy of cancer, 4, 1-11.

CAR Construction :

Fig.6 Drozitumab (DRO) with anti-Fc antibody treatment induces apoptosis in the sensitive RMS cells.

The sensitive Rh18 cells were treated with drozitumab or a 1:1 ratio of drozitumab anti-Fc antibodies at the indicated doses for 72 hours prior to the viability assay (top).

Kang, Z., Chen, J. J., Yu, Y., Li, B., Sun, S. Y., Zhang, B., & Cao, L. (2011). Drozitumab, a Human Antibody to Death Receptor 5, Has Potent Antitumor Activity against Rhabdomyosarcoma with the Expression of Caspase-8 Predictive of ResponsePreclinical Evaluation of DR5 Antibody Drozitumab in RMS. Clinical Cancer Research, 17(10), 3181-3192.

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Fig.7 The cell surface expression of DR4 and DR5 was analyzed by FACS in selected TRAIL and DR5 resistant (R) or sensitive (S) cells.

TRAIL reduces RMS cell viability mediated via the DR5 receptor.

Kang, Z., Chen, J. J., Yu, Y., Li, B., Sun, S. Y., Zhang, B., & Cao, L. (2011). Drozitumab, a Human Antibody to Death Receptor 5, Has Potent Antitumor Activity against Rhabdomyosarcoma with the Expression of Caspase-8 Predictive of ResponsePreclinical Evaluation of DR5 Antibody Drozitumab in RMS. Clinical Cancer Research, 17(10), 3181-3192.

CAR Construction :

Fig.1 Flow Cytometry analysis of cell surface expression of Apo2L/TRAIL death receptors in drozitumab-sensitive MDA-MB-231-TXSA cells versus resistant MDA-MB-231-droz-R cells.

Graphs were obtained after staining with anti human DR5 monoclonal antibodies.

Zinonos, I., Labrinidis, A., Liapis, V., Hay, S., Panagopoulos, V., Denichilo, M., ... & Evdokiou, A. (2014). Doxorubicin overcomes resistance to drozitumab by antagonizing inhibitor of apoptosis proteins (IAPs). Anticancer Research, 34(12), 7007-7020.