A new approach to cancer vaccination yields more powerful T cells to fight multiple different cancers

Good news! Cancer is history (soon)!

"... have developed a new way to amplify the T-cell response to mRNA vaccines — an advance that could lead to much more powerful cancer vaccines and stronger protection against infectious diseases.

Most vaccines generate both antibodies and T cells that can target the vaccine antigen by activating antigen-presenting cells, such as dendritic cells. 

In this study, the researchers boosted the T-cell response with a new type of vaccine adjuvant (a material that can help stimulate the immune system). The new adjuvant consists of mRNA molecules encoding genes that turn on immune signaling pathways and promote a supercharged T-cell response. 

In studies in mice, this mRNA-encoded adjuvant enabled the immune system to completely eradicate most tumors, either on its own or delivered along with a tumor antigen. ..."

From the abstract:

"Although immunotherapy has benefited a subset of persons with cancer, its broader efficacy remains limited, primarily because of an immunosuppressive tumor microenvironment characterized by insufficient numbers of functional tumor-specific T cells, antigen-presenting cells (APCs) and tumor-infiltrating lymphocytes.

Here we engineer immune cells in the tumor microenvironment using lipid nanoparticles (LNPs) to deliver immune-remodeling mRNAs (IR-mRNAs) encoding NF-κB-inducing kinase or interferon regulatory factor 8.

These IR-mRNAs activate APCs in tumors, significantly increasing activated type 1 conventional dendritic cells, immunostimulatory cytokines and priming antitumor CD8+ T cells.

IR-mRNAs encapsulated in LNPs elicited durable antitumor responses in multiple syngeneic mouse tumor models through both intratumoral and intravenous delivery.

Coadministration of IR-mRNA and ovalbumin mRNA elicited a ~10-fold increase in antigen-specific CD8+ T cell responses, sustained long-term memory and effectively prevented tumor growth in vaccinated mice.

Additionally, coadministration of IR-mRNA and hemagglutinin mRNA enhanced the humoral response ~5-fold and the cellular response ~15-fold, underscoring their potential as adjuvants for boosting adaptive immunity."

A new approach to cancer vaccination yields more powerful T cells | MIT News | Massachusetts Institute of Technology "Using immune-remodeling mRNA molecules, researchers generated T cells that can slow tumor growth and, in some cases, eradicate tumors."

Immune-remodeling mRNAs expressing IRF8 or NIK generate durable antitumor immunity in multiple cancer models (no public access)