Transfer of mRNA encoding recombinant immunoreceptors reprograms CD4+ and CD8+ T cells for use in the adoptive immunotherapy of cancer

Birkholz, Katrin; Hombach, Andreas; Krug, Christian; Reuter, Sabrina; Kershaw, Michael H.; Kämpgen, Eckhart; Schuler, Gerold; Abken, Hinrich; Schaft, Niels; Dörrie, Jan

doi:10.1038/gt.2008.189

Cited by 104 publications

(80 citation statements)

References 42 publications

(53 reference statements)

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“…1A and data not shown). This prolonged high transgene persistence was different from most reports of peak and duration of expression of a surface antigen after mRNA transfection (Birkholz et al, 2009;Rabinovich et al, 2009;Yoon et al, 2009;Li et al, 2010), possibly due to our optimized IVT vector and RNA production (data not shown). In parallel, we assessed the cytotoxic potential of CAR-expressing T cells in vitro with a flow cytometry-based killing assay.…”

Section: Generation Of Car-expressing T Cells By Mrna Transfection Recontrasting

confidence: 52%

“…More recently, CARs against the Her2/neu antigen were introduced into T cells by mRNA electroporation and were found to be more effective than Her2/neu antibodies in a breast cancer xenograft model (Yoon et al, 2009). Other human target antigens of CARs introduced into T cells by mRNA electroporation include carcinoembryonic antigen and ErbB2 (Birkholz et al, 2009). Although a number of studies have demonstrated efficacy using this approach in solid tumors after intratumoral injection or in local injection intraperitoneal models, no group has demonstrated similar success in disseminated leukemia preclinical models, possibly due to the difficulty in generating efficacy in a disseminated model with a transient expression system (Rabinovich et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Treatment of Advanced Leukemia in Mice with mRNA Engineered T Cells

et al. 2011

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Cytotoxic T lymphocytes (CTLs) modified with chimeric antigen receptors (CARs) for adoptive immunotherapy of hematologic malignancies are effective in preclinical models and are being tested in several clinical trials. Although CTLs bearing stably expressed CARs generated by integrating viral vectors are efficacious and have potential long-term persistence, this mechanism of CAR expression can potentially result in significant toxicity. T cells were electroporated with an optimized in vitro transcribed RNA encoding a CAR against CD19. These RNA CAR CTLs were then tested in vitro and in vivo for efficacy. We found that T cells expressing an anti-CD19 CAR introduced by electroporation with optimized mRNA were potent and specific killers of CD19 target cells. CD19

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Section: Generation Of Car-expressing T Cells By Mrna Transfection Recontrasting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Treatment of Advanced Leukemia in Mice with mRNA Engineered T Cells

et al. 2011

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“…Although transient, mRNA transfection can drive functional expression of the introduced genes up to 5-7 days and more. [32][33][34][35][36] The use of mRNA entirely obviates the risk of cellular transformation and allows the co-introduction of several genes as pre-defined mixtures, which is often limited with other gene delivery vehicles.…”

Section: Introductionmentioning

confidence: 99%

Adoptive Transfer of mRNA-Transfected T Cells Redirected against Diabetogenic CD8 T Cells Can Prevent Diabetes

et al. 2017

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“…With this rationale, RNA-modified CAR T cells were applied with some anti-tumor efficacy so far [113]; however, repeated doses of CAR T cells produced an anti-CAR response due to xenogenic CAR components [114]. Upon activation of CAR T cells, the time of CAR expression is moreover shortened thereby limiting a potential side effect on healthy tissues [115].…”

Section: (Iv) Transient Car Expressionmentioning

confidence: 99%

CARs on the Highway: Chimeric Antigen Receptor Modified T Cells for the Adoptive Cell Therapy of Malignant Diseases

Holzinger¹,

Abken²

2017

Immunotherapy - Myths, Reality, Ideas, Future

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Adoptive therapy of malignant diseases by chimeric antigen receptor (CAR) redirected T cells takes advantage of the patient's own immune system to recognize and destroy cancer cells. This is impressively demonstrated by the induction of complete and lasting remissions of leukemia with CAR-engineered T cells in early phase trials. Recent developments in optimizing the CAR design, in the recognition of target cells and the production of modified cells for clinical use, have paved the path for a broader application than currently explored. The chapter reviews the differences in CAR design, the success in the treatment of hematologic malignancies, the challenges in treating solid cancer, the treatment-related toxicities, and strategies to improve safety of CAR T cell therapy. Challenges for future applications are discussed.

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Transfer of mRNA encoding recombinant immunoreceptors reprograms CD4+ and CD8+ T cells for use in the adoptive immunotherapy of cancer

Cited by 104 publications

References 42 publications

Treatment of Advanced Leukemia in Mice with mRNA Engineered T Cells

Treatment of Advanced Leukemia in Mice with mRNA Engineered T Cells

Adoptive Transfer of mRNA-Transfected T Cells Redirected against Diabetogenic CD8 T Cells Can Prevent Diabetes

CARs on the Highway: Chimeric Antigen Receptor Modified T Cells for the Adoptive Cell Therapy of Malignant Diseases

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