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

被引：52

作者：

Feldmann, Anja ^{[1
]}

Hoffmann, Anja ^{[1
]}

Bergmann, Ralf ^{[1
,2
]}

Koristka, Stefanie ^{[1
]}

Berndt, Nicole ^{[1
]}

Arndt, Claudia ^{[1
]}

Rodrigues Loureiro, Liliana ^{[1
]}

Kittel-Boselli, Enrico ^{[3
]}

Mitwasi, Nicola ^{[1
]}

Kegler, Alexandra ^{[1
]}

Lamprecht, Chris ^{[1
,4
]}

Gonzalez Soto, Karla Elizabeth ^{[1
]}

Bachmann, Michael ^{[1
,3
,5
,6
,7
,8
,9
,10
,11
]}

机构：

[1] Helmholtz Zentrum Dresden Rossendorf HZDR, Inst Radiopharmaceut Canc Res, Dept Radioimmunol, Dresden, Germany

[2] Semmelweis Univ, Dept Biophys & Radiat Biol, Budapest, Hungary

[3] Tech Univ Dresden, Univ Hosp Carl Gustav Carus Dresden, Univ Canc Ctr UCC, Tumor Immunol, Dresden, Germany

[4] Univ Hosp Carl Gustav Carus Dresden, Ctr Clin Neurosci, Dept Neurol, Dresden, Germany

[5] Natl Ctr Tumor Dis NCT, Dresden, Germany

[6] German Canc Res Ctr, Heidelberg, Germany

[7] Tech Univ Dresden, Fac Med, Dresden, Germany

[8] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dresden, Germany

[9] Helmholtz Zentrum Dresden Rossendorf HZDR, Dresden, Germany

[10] German Canc Res Ctr, Heidelberg, Germany

[11] German Canc Consortium DKTK, Dresden, Germany

来源：

ONCOIMMUNOLOGY | 2020年 / 9卷 / 01期

关键词：

Chimeric antigen receptor (CAR); T cell therapy; tumor immunotherapy; adaptor CAR platform; combinatorial gated targeting; CANCER; IMMUNOTHERAPY; LYMPHOCYTES; EXPRESSION; STRATEGY;

D O I：

10.1080/2162402X.2020.1785608

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

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.

引用

页数：15

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