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

共 52 条

[41] Development of novel target modules for retargeting of UniCAR T cells to GD2 positive tumor cells [J].

Mitwasi, Nicola ;

Feldmann, Anja ;

Bergmann, Ralf ;

Berndt, Nicole ;

Arndt, Claudia ;

Koristka, Stefanie ;

Kegler, Alexandra ;

Jureczek, Justyna ;

Hoffmann, Anja ;

Ehninger, Armin ;

Cartellieri, Marc ;

Albert, Susann ;

Rossig, Claudia ;

Ehninger, Gerhard ;

Pietzsch, Jens ;

Steinbach, Joerg ;

Bachmann, Michael .

ONCOTARGET, 2017, 8 (65) :108584-108603

[42] Case Report of a Serious Adverse Event Following the Administration of T Cells Transduced With a Chimeric Antigen Receptor Recognizing ERBB2 [J].

Morgan, Richard A. ;

Yang, James C. ;

Kitano, Mio ;

Dudley, Mark E. ;

Laurencot, Carolyn M. ;

Rosenberg, Steven A. .

MOLECULAR THERAPY, 2010, 18 (04) :843-851

[43] Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma [J].

Neelapu, S. S. ;

Locke, F. L. ;

Bartlett, N. L. ;

Lekakis, L. J. ;

Miklos, D. B. ;

Jacobson, C. A. ;

Braunschweig, I. ;

Oluwole, O. O. ;

Siddiqi, T. ;

Lin, Y. ;

Timmerman, J. M. ;

Stiff, P. J. ;

Friedberg, J. W. ;

Flinn, I. W. ;

Goy, A. ;

Hill, B. T. ;

Smith, M. R. ;

Deol, A. ;

Farooq, U. ;

McSweeney, P. ;

Munoz, J. ;

Avivi, I. ;

Castro, J. E. ;

Westin, J. R. ;

Chavez, J. C. ;

Ghobadi, A. ;

Komanduri, K. V. ;

Levy, R. ;

Jacobsen, E. D. ;

Witzig, T. E. ;

Reagan, P. ;

Bot, A. ;

Rossi, J. ;

Navale, L. ;

Jiang, Y. ;

Aycock, J. ;

Elias, M. ;

Chang, D. ;

Wiezorek, J. ;

Go, W. Y. .

NEW ENGLAND JOURNAL OF MEDICINE, 2017, 377 (26) :2531-2544

[44] A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma [J].

O'Rourke, Donald M. ;

Nasrallah, MacLean P. ;

Desai, Arati ;

Melenhorst, Jan J. ;

Mansfield, Keith ;

Morrissette, Jennifer J. D. ;

Martinez-Lage, Maria ;

Brem, Steven ;

Maloney, Eileen ;

Shen, Angela ;

Isaacs, Randi ;

Mohan, Suyash ;

Plesa, Gabriela ;

Lacey, Simon F. ;

Navenot, Jean-Marc ;

Zheng, Zhaohui ;

Levine, Bruce L. ;

Okada, Hideho ;

June, Carl H. ;

Brogdon, Jennifer L. ;

Maus, Marcela V. .

SCIENCE TRANSLATIONAL MEDICINE, 2017, 9 (399)

[45] Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies [J].

Rodgers, David T. ;

Mazagova, Magdalena ;

Hampton, Eric N. ;

Cao, Yu ;

Ramadoss, Nitya S. ;

Hardy, Ian R. ;

Schulman, Andrew ;

Du, Juanjuan ;

Wang, Feng ;

Singer, Oded ;

Ma, Jennifer ;

Nunez, Vanessa ;

Shen, Jiayin ;

Woods, Ashley K. ;

Wright, Timothy M. ;

Schultz, Peter G. ;

Kim, Chan Hyuk ;

Young, Travis S. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2016, 113 (04) :E459-E468

[46] Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma [J].

Schuster, Stephen J. ;

Bishop, Michael R. ;

Tam, Constantine S. ;

Waller, Edmund K. ;

Borchmann, Peter ;

McGuirk, Joseph P. ;

Jaeger, Ulrich ;

Jaglowski, Samantha ;

Andreadis, Charalambos ;

Westin, Jason R. ;

Fleury, Isabelle ;

Bachanova, Veronika ;

Foley, S. Ronan ;

Ho, P. Joy p ;

Mielke, Stephan ;

Magenau, John M. ;

Holte, Harald ;

Pantano, Serafino ;

Pacaud, Lida B. ;

Awasthi, Rakesh ;

Chu, Jufen ;

Anak, Ozlem ;

Salles, Gilles ;

Maziarz, Richard T. .

NEW ENGLAND JOURNAL OF MEDICINE, 2019, 380 (01) :45-56

[47] CARs versus BiTEs: A Comparison between T Cell-Redirection Strategies for Cancer Treatment [J].

Slaney, Clare Y. ;

Wang, Pin ;

Darcy, Phillip K. ;

Kershaw, Michael H. .

CANCER DISCOVERY, 2018, 8 (08) :924-934

[48] Redirecting Gene-Modified T Cells toward Various Cancer Types Using Tagged Antibodies [J].

Tamada, Koji ;

Geng, Degui ;

Sakoda, Yukimi ;

Bansal, Navneeta ;

Srivastava, Ratika ;

Li, Zhaoyang ;

Davila, Eduardo .

CLINICAL CANCER RESEARCH, 2012, 18 (23) :6436-6445

[49] Targeted cancer immunotherapy via combination of designer bispecific antibody and novel gene-engineered T cells [J].

Urbanska, Katarzyna ;

Lynn, Rachel C. ;

Stashwick, Caitlin ;

Thakur, Archana ;

Lum, Lawrence G. ;

Powell, Daniel J., Jr. .

JOURNAL OF TRANSLATIONAL MEDICINE, 2014, 12

[50] A Universal Strategy for Adoptive Immunotherapy of Cancer through Use of a Novel T-cell Antigen Receptor [J].

Urbanska, Katarzyna ;

Lanitis, Evripidis ;

Poussin, Mathilde ;

Lynn, Rachel C. ;

Gavin, Brian P. ;

Kelderman, Sander ;

Yu, Jason ;

Scholler, Nathalie ;

Powell, Daniel J., Jr. .

CANCER RESEARCH, 2012, 72 (07) :1844-1852

← 1 2 3 4 5 6 →