Researchers at Ohio State University have found a way to increase the activation of T cells inside tumors, which improves the effectiveness of their interactions with a new antibody therapy that is currently being evaluated in clinical trials.
The researchers developed nanoparticles from a compound that is present in cell membranes and used them to deliver messenger RNA (mRNA) directly into cells. The mRNA was developed to carry instructions for molecules that are normally produced by T cells as part of the immune response.
The researchers injected the nanoparticles directly into the tumors of mouse models of certain cancers to stimulate T cells to generate specific receptors on their surfaces, amplifying their expression of those receptors. 6 hours after injecting the nanoparticles, the researchers delivered experimental monoclonal antibodies, which bound to the T-cells receptors allowing them to attack the cancer cells.
In mouse models of B cell lymphoma, after treatment with the nanoparticles and monoclonal antibodies, 6 of the 10 mice were free of lymphoma tumors. The researchers later injected lymphoma cells into the mice that were tumor-free and found the lymphoma cells did not survive for long enough to form solid tumors. The treatment was also shown to be effective at amplifying the immune response in mouse models of melanoma when combined with existing drugs.
“T cells are very important for fighting a lot of diseases – not just cancer – and it is really difficult to modulate their function,” said associate professor Yizhou Dong, senior author of the study. “After injections of therapeutically relevant mRNA, the T cells decorate their surfaces with receptors, and that enables their additional functions: proliferating, recruiting other immune cells and production of helpful proteins. When T cells significantly increase those receptors, antibodies can react with the receptors and carry out all the functions we know that interaction can produce.”
The researchers believe their new technique could be used to enhance the effectiveness of immunotherapy in human cancer patients. They are now testing further materials to see if it is possible to deliver even mRNA to even more T cells to improve efficiency. “Ultimately, we hope that for certain cancers, this may help produce stronger immune system function by inducing anti-tumor immunity,” said Dong.
You can read more about the study in the paper – Biomimetic nanoparticles deliver mRNAs encoding costimulatory receptors and enhance T cell mediated cancer immunotherapy – which was recently published in Nature Communications. DOI: 10.1038/s41467-021-27434-x