Back to Search
Start Over
Biomimetic nanoparticles deliver mRNAs encoding costimulatory receptors and enhance T cell mediated cancer immunotherapy.
- Source :
-
Nature communications [Nat Commun] 2021 Dec 14; Vol. 12 (1), pp. 7264. Date of Electronic Publication: 2021 Dec 14. - Publication Year :
- 2021
-
Abstract
- Antibodies targeting costimulatory receptors of T cells have been developed for the activation of T cell immunity in cancer immunotherapy. However, costimulatory molecule expression is often lacking in tumor-infiltrating immune cells, which can impede antibody-mediated immunotherapy. Here, we hypothesize that delivery of costimulatory receptor mRNA to tumor-infiltrating T cells will enhance the antitumor effects of antibodies. We first design a library of biomimetic nanoparticles and find that phospholipid nanoparticles (PL1) effectively deliver costimulatory receptor mRNA (CD137 or OX40) to T cells. Then, we demonstrate that the combination of PL1-OX40 mRNA and anti-OX40 antibody exhibits significantly improved antitumor activity compared to anti-OX40 antibody alone in multiple tumor models. This treatment regimen results in a 60% complete response rate in the A20 tumor model, with these mice being resistant to rechallenge by A20 tumor cells. Additionally, the combination of PL1-OX40 mRNA and anti-OX40 antibody significantly boosts the antitumor immune response to anti-PD-1 + anti-CTLA-4 antibodies in the B16F10 tumor model. This study supports the concept of delivering mRNA encoding costimulatory receptors in combination with the corresponding agonistic antibody as a strategy to enhance cancer immunotherapy.<br /> (© 2021. The Author(s).)
- Subjects :
- Animals
Biomimetic Materials chemistry
Drug Delivery Systems
Glycolipids administration & dosage
Glycolipids chemistry
Lymphocytes, Tumor-Infiltrating metabolism
Mice
Nanoparticles chemistry
Neoplasms, Experimental immunology
Neoplasms, Experimental therapy
Phospholipids administration & dosage
Phospholipids chemistry
RNA, Messenger chemistry
Receptors, OX40 antagonists & inhibitors
Receptors, OX40 genetics
Receptors, OX40 immunology
Receptors, OX40 metabolism
T-Lymphocytes metabolism
Tumor Necrosis Factor Receptor Superfamily, Member 9 antagonists & inhibitors
Tumor Necrosis Factor Receptor Superfamily, Member 9 genetics
Tumor Necrosis Factor Receptor Superfamily, Member 9 immunology
Tumor Necrosis Factor Receptor Superfamily, Member 9 metabolism
Biomimetic Materials administration & dosage
Immunotherapy methods
Lymphocytes, Tumor-Infiltrating immunology
Nanoparticles administration & dosage
RNA, Messenger administration & dosage
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 34907171
- Full Text :
- https://doi.org/10.1038/s41467-021-27434-x