T cells armed with C-X-C chemokine receptor type 6 enhance adoptive cell therapy for pancreatic tumours

被引：126

作者：

Lesch, Stefanie ^{[1
,2
]}

Blumenberg, Viktoria ^{[1
,2
,3
]}

Stoiber, Stefan ^{[1
,2
]}

Gottschlich, Adrian ^{[1
,2
]}

Ogonek, Justyna ^{[1
,2
]}

Cadilha, Bruno L. ^{[1
,2
]}

Dantes, Zahra ^{[4
]}

Rataj, Felicitas ^{[1
,2
]}

Dorman, Klara ^{[1
,2
]}

Lutz, Johannes ^{[1
,2
]}

Karches, Clara H. ^{[1
,2
]}

Heise, Constanze ^{[1
,2
]}

Kurzay, Mathias ^{[1
,2
]}

Larimer, Benjamin M. ^{[5
]}

Grassmann, Simon ^{[1
,2
]}

Rapp, Moritz ^{[1
,2
]}

Nottebrock, Alessia ^{[1
,2
]}

Kruger, Stephan ^{[1
,2
,3
]}

Tokarew, Nicholas ^{[1
,2
]}

Metzger, Philipp ^{[1
,2
]}

Hoerth, Christine ^{[1
,2
]}

Benmebarek, Mohamed-Reda ^{[1
,2
]}

Dhoqina, Dario ^{[1
,2
]}

Grunmeier, Ruth ^{[1
,2
]}

Seifert, Matthias ^{[1
,2
]}

Oener, Arman ^{[1
,2
]}

Umut, Oyku ^{[1
,2
]}

Joaquina, Sandy ^{[6
,7
]}

Vimeux, Lene ^{[6
,7
]}

Tran, Thi ^{[7
,8
]}

Hank, Thomas ^{[9
,10
]}

Baba, Taisuke ^{[9
,10
]}

Huynh, Duc ^{[1
,2
]}

Megens, Remco T. A. ^{[11
,12
]}

Janssen, Klaus-Peter ^{[13
]}

Jastroch, Martin ^{[14
,15
]}

Lamp, Daniel ^{[14
,15
]}

Ruehland, Svenja ^{[16
]}

Di Pilato, Mauro ^{[17
]}

Pruessmann, Jasper N. ^{[17
]}

Thomas, Moritz ^{[18
,19
]}

Marr, Carsten ^{[18
]}

Ormanns, Steffen ^{[20
]}

Reischer, Anna ^{[3
]}

Hristov, Michael ^{[11
]}

Tartour, Eric ^{[7
,8
,21
]}

Donnadieu, Emmanuel ^{[6
,7
]}

Rothenfusser, Simon ^{[1
,2
,22
]}

Duewell, Peter ^{[23
]}

Konig, Lars M. ^{[1
,2
]}

机构：

[1] Ludwig Maximilians Univ Munchen, Univ Hosp, Ctr Integrated Prot Sci Munich CIPS M, Munich, Germany

[2] Ludwig Maximilians Univ Munchen, Univ Hosp, Div Clin Pharmacol, Dept Med 4, Munich, Germany

[3] Ludwig Maximilians Univ Munchen, Univ Hosp, Dept Med 3, Munich, Germany

[4] Tech Univ Munich, Klin & Poliklin Innere Med 2, Klinikum Rechts Isar, Munich, Germany

[5] Massachusetts Gen Hosp, Dept Radiol, Ctr Precis Imaging, Boston, MA USA

[6] Univ Paris, CNRS, Inst Cochin, INSERM, Paris, France

[7] Equipe Labellisee Ligue Canc, Toulouse, France

[8] Univ Paris, PARCC, INSERM, U970, Paris, France

[9] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA

[10] Harvard Med Sch, Boston, MA 02115 USA

[11] Ludwig Maximilians Univ Munchen, Univ Hosp, Inst Cardiovasc Prevent IPEK, Munich, Germany

[12] Maastricht Univ, Cardiovasc Res Inst Maastricht CARIM, Dept Biomed Engn, Maastricht, Netherlands

[13] Tech Univ Munich, Dept Surg, Klinikum Rechts Isar, Munich, Germany

[14] Helmholtz Zentrum Munchen, Helmholtz Diabet Ctr, Neuherberg, Germany

[15] Helmholtz Zentrum Munchen, German Diabet Ctr DZD, Neuherberg, Germany

[16] Ludwig Maximilians Univ Munchen, Dept Biol 2, LMU Bioctr, Munich, Germany

[17] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA

[18] German Res Ctr Environm Hlth, Inst Computat Biol, Helmholtz Zentrum Munchen, Neuherberg, Germany

[19] Tech Univ Munich, Sch Life Sci Weihenstephan, Freising Weihenstephan, Germany

[20] Ludwig Maximilians Univ Munchen, Inst Pathol, Munich, Germany

[21] Hop Europeen Georges Pompidou, AP HP, Serv Immunol Biol, Paris, France

[22] German Res Ctr Environm Hlth HMGU, Einheit Klin Pharmakol EKLiP, Helmholtz Zentrum Munchen, Neuherberg, Germany

[23] Univ Bonn, Inst Innate Immun, Bonn, Germany

[24] German Canc Res Ctr, Dept Translat Immunotherapy, Heidelberg, Germany

[25] Tech Univ Munich, Ctr Funct Prot Assemblies CPA, Garching, Germany

[26] German Ctr Translat Canc Res DKTK, Munich, Germany

来源：

NATURE BIOMEDICAL ENGINEERING | 2021年 / 5卷 / 11期

基金：

欧洲研究理事会; 欧盟地平线“2020”;

关键词：

CHIMERIC ANTIGEN RECEPTOR; CXC CHEMOKINE; INFILTRATING LYMPHOCYTES; IMMUNE CELLS; IMMUNOTHERAPY; CANCER; RECRUITMENT; EXPRESSION; LOCALIZATION; TRANSDUCTION;

D O I：

10.1038/s41551-021-00737-6

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

Forced expression of C-X-C chemokine receptor type 6 in antigen-specific T cells enhanced the recognition and lysis of pancreatic cancer cells and the efficacy of adoptive cell therapy for pancreatic cancer. The efficacy of adoptive cell therapy for solid tumours is hampered by the poor accumulation of the transferred T cells in tumour tissue. Here, we show that forced expression of C-X-C chemokine receptor type 6 (whose ligand is highly expressed by human and murine pancreatic cancer cells and tumour-infiltrating immune cells) in antigen-specific T cells enhanced the recognition and lysis of pancreatic cancer cells and the efficacy of adoptive cell therapy for pancreatic cancer. In mice with subcutaneous pancreatic tumours treated with T cells with either a transgenic T-cell receptor or a murine chimeric antigen receptor targeting the tumour-associated antigen epithelial cell adhesion molecule, and in mice with orthotopic pancreatic tumours or patient-derived xenografts treated with T cells expressing a chimeric antigen receptor targeting mesothelin, the T cells exhibited enhanced intratumoral accumulation, exerted sustained anti-tumoral activity and prolonged animal survival only when co-expressing C-X-C chemokine receptor type 6. Arming tumour-specific T cells with tumour-specific chemokine receptors may represent a promising strategy for the realization of adoptive cell therapy for solid tumours.

引用

页码：1246 / 1260

页数：21

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