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Membrane-proximal external region is a superior target for mediating effector activity of HIV-1 specific chimeric antigen receptor modified T cells

biorxiv. 2020; 
Emiko Kranz, Joshua Chan,  Maya Hashimoto,  Toshio Kanazawa,  Hanlu Wang, Masakazu Kamata
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摘要

The use of chimeric antigen receptor modified-T (CAR-T) cells in adoptive immunotherapy has been popularized through recent success in the field of cancer treatment research. CD4ζ CAR, which targets HIV-1-infected cells, has been developed and evaluated in patients. Though well-tolerated for over a decade, efficacy was disappointingly limited. This result encourages us to develop a novel CAR more effective than CD4ζ CAR. To quantitatively compare anti-HIV-1 activity of different CAR constructs in a highly sensitive and reproducible manner, we developed a multicolor flow cytometry method for assessing anti-HIV-1 effector T-cell activity. “Target” Jurkat cells inducibly expressing an HIV-1HXBC2 envelope pr... More

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