Versatile chimeric antigen receptor platform for controllable and combinatorial T cell therapy

OncoImmunology

Anja Hoffmann¹  Claudia Arndt¹  Michael Bachmann¹  Karla Elizabeth González Soto¹  Nicola Mitwasi¹  Anja Feldmann¹  Liliana Rodrigues Loureiro¹  Stefanie Koristka¹  Alexandra Kegler¹  Nicole Berndt¹  Ralf Bergmann¹  Chris Lamprecht¹  Enrico Kittel-Boselli² 

[1] Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR);Tumor Immunology, University Cancer Center (UCC), University Hospital Carl Gustav Carus Dresden;

关键词: chimeric antigen receptor (car);    t cell therapy;    tumor immunotherapy;    adaptor car platform;    combinatorial gated targeting;   

DOI  :  10.1080/2162402X.2020.1785608

来源: DOAJ

【 摘 要 】

Chimeric antigen receptor (CAR) T cells show remarkable therapeutic effects in some hematological malignancies. However, CAR T cells can also cause life-threatening side effects. In order to minimize off-target and on-target/off-tumor reactions, improve safety, enable controllability, provide high flexibility, and increase tumor specificity, we established a novel humanized artificial receptor platform termed RevCARs. RevCAR genes encode for small surface receptors lacking any antigen-binding moiety. Steering of RevCAR T cells occurs via bispecific targeting molecules (TMs). The small size of RevCAR-encoding genes allows the construction of polycistronic vectors. Here, we demonstrate that RevCAR T cells efficiently kill tumor cells, can be steered by TMs, flexibly redirected against multiple targets, and used for combinatorial targeting following the “OR” and “AND” gate logic.

【 授权许可】

Unknown