Title |
Intratumoral Delivery of TriMix mRNA Results in T-cell Activation by Cross-Presenting Dendritic Cells
|
---|---|
Published in |
Cancer Immunology Research, February 2016
|
DOI | 10.1158/2326-6066.cir-15-0163 |
Pubmed ID | |
Authors |
Sandra Van Lint, Dries Renmans, Katrijn Broos, Lode Goethals, Sarah Maenhout, Daphné Benteyn, Cleo Goyvaerts, Stephanie Du Four, Kevin Van der Jeught, Lukasz Bialkowski, Véronique Flamand, Carlo Heirman, Kris Thielemans, Karine Breckpot |
Abstract |
Modulating the activity of tumor-infiltrating dendritic cells (TiDC) provides opportunities for novel cancer interventions. In this article, we report on our study of the uptake of mRNA by CD8α(+) cross-presenting TiDCs upon its intratumoral (i.t.) delivery. We exploited this property to deliver mRNA encoding the costimulatory molecule CD70, the activation stimuli CD40 ligand, and constitutively active Toll-like receptor 4, referred to as TriMix mRNA. We show that TiDCs are reprogrammed to mature antigen-presenting cells that migrate to tumor-draining lymph nodes (TDLN). TriMix stimulated antitumor T-cell responses to spontaneously engulfed cancer antigens, including a neoepitope. We show in various mouse cancer models that i.t. delivery of TriMix mRNA results in systemic therapeutic antitumor immunity. Finally, we show that the induction of antitumor responses critically depends on TiDCs, whereas it only partially depends on TDLNs. As such, we provide a platform and a mechanistic rationale for the clinical testing of i.t. administration of TriMix mRNA. Cancer Immunol Res; 4(2); 146-56. ©2015 AACR. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | <1% |
France | 1 | <1% |
Unknown | 108 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 32 | 29% |
Researcher | 15 | 14% |
Student > Doctoral Student | 11 | 10% |
Student > Bachelor | 8 | 7% |
Other | 7 | 6% |
Other | 12 | 11% |
Unknown | 25 | 23% |
Readers by discipline | Count | As % |
---|---|---|
Immunology and Microbiology | 21 | 19% |
Agricultural and Biological Sciences | 15 | 14% |
Biochemistry, Genetics and Molecular Biology | 13 | 12% |
Medicine and Dentistry | 10 | 9% |
Pharmacology, Toxicology and Pharmaceutical Science | 9 | 8% |
Other | 11 | 10% |
Unknown | 31 | 28% |