| Literature DB >> 26830879 |
Kole T Roybal1, Levi J Rupp1, Leonardo Morsut1, Whitney J Walker1, Krista A McNally1, Jason S Park1, Wendell A Lim2.
Abstract
T cells can be re-directed to kill cancer cells using chimeric antigen receptors (CARs) or T cell receptors (TCRs). This approach, however, is constrained by the rarity of tumor-specific single antigens. Targeting antigens also found on bystander tissues can cause life-threatening adverse effects. A powerful way to enhance ON-target activity of therapeutic T cells is to engineer them to require combinatorial antigens. Here, we engineer a combinatorially activated T cell circuit in which a synthetic Notch receptor for one antigen induces the expression of a CAR for a second antigen. These dual-receptor AND-gate T cells are only armed and activated in the presence of dual antigen tumor cells. These T cells show precise therapeutic discrimination in vivo-sparing single antigen "bystander" tumors while efficiently clearing combinatorial antigen "disease" tumors. This type of precision dual-receptor circuit opens the door to immune recognition of a wider range of tumors. VIDEO ABSTRACT.Entities:
Mesh：
Substances：
Year: 2016 PMID： 26830879 PMCID： PMC4752902 DOI： 10.1016/j.cell.2016.01.011
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582