Cryogel-supported stem cell factory for customized sustained release of bispecific antibodies for cancer immunotherapy

被引：52

作者：

Aliperta, Roberta ^{[1
]}

Welzel, Petra B. ^{[2
]}

Bergmann, Ralf ^{[1
]}

Freudenberg, Uwe ^{[2
]}

Berndt, Nicole ^{[1
]}

Feldmann, Anja ^{[1
]}

Arndt, Claudia ^{[1
]}

Koristka, Stefanie ^{[1
]}

Stanzione, Marcello ^{[3
]}

Cartellieri, Marc ^{[4
,5
]}

Ehninger, Armin ^{[6
]}

Ehninger, Gerhard ^{[7
,8
,9
]}

Werner, Carsten ^{[2
,10
]}

Pietzsch, Jens ^{[1
,11
]}

Steinbach, Joerg ^{[1
,11
]}

Bornhaeuser, Martin ^{[7
,8
,9
,10
]}

Bachmann, Michael P. ^{[1
,8
,9
,10
]}

机构：

[1] Helmholtz Zentrum Dresden Rossendorf, Inst Radiopharmaceut Canc Res, Bautzner Landstr 400, D-01328 Dresden, Germany

[2] Leibniz Inst Polymer Res Dresden IPF, Hohe Str 6, D-01069 Dresden, Germany

[3] Tech Univ Dresden, Inst Physiol Chem, Fetscherstr 74, D-01307 Dresden, Germany

[4] Cellex Patient Treatment GmbH, Tatzberg 47, D-01307 Dresden, Germany

[5] Tech Univ Dresden, UCC, Tumorimmunol, Fetscherstr 74, D-01307 Dresden, Germany

[6] GEMoaB Monoclonals GmbH, Tatzberg 47, D-01307 Dresden, Germany

[7] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Med Clin & Policlin 1, Fetscherstr 4, D-01307 Dresden, Germany

[8] DKTK, German Consortium Translat Canc Res, Dresden, Germany

[9] Carl Gustav Carus TU Dresden, Nat Ctr Tumor Dis NCT, Dresden, Germany

[10] Tech Univ Dresden, DFG Ctr Regenerat Therapies Dresden, Fetscherstr 105, D-01307 Dresden, Germany

[11] Tech Univ Dresden, Sch Sci, Dept Chem & Food Chem, D-01069 Dresden, Germany

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

关键词：

ANTIGEN; MEMBERS; FAMILY; TRIAL;

D O I：

10.1038/srep42855

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Combining stem cells with biomaterial scaffolds provides a promising strategy for the development of drug delivery systems. Here we propose an innovative immunotherapeutic organoid by housing human mesenchymal stromal cells (MSCs), gene-modified for the secretion of an anti-CD33-anti-CD3 bispecific antibody (bsAb), in a small biocompatible star-shaped poly(ethylene glycol)-heparin cryogel scaffold as a transplantable and low invasive therapeutic machinery for the treatment of acute myeloid leukemia (AML). The macroporous biohybrid cryogel platform displays effectiveness in supporting proliferation and survival of bsAb-releasing-MSCs overtime in vitro and in vivo, avoiding cell loss and ensuring a constant release of sustained and detectable levels of bsAb capable of triggering T-cell-mediated anti-tumor responses and a rapid regression of CD33(+) AML blasts. This therapeutic device results as a promising and safe alternative to the continuous administration of short-lived immunoagents and paves the way for effective bsAb-based therapeutic strategies for future tumor treatments.

引用

页数：16

共 49 条

[1]

Bispecific antibody releasing-mesenchymal stromal cell machinery for retargeting T cells towards acute myeloid leukemia blasts [J].