Of the active mRNA cancer vaccine clinical trials, there are 4 that are LNP-based, 13 that are Lipoplex formulation-based and 19 mRNA dendritic cell cancer vaccines. mRNA cancer vaccines are promising therapeutic candidates due to having the potential for inducing both humoral and cell-mediated immunity. Some of the known advantages of using mRNA vaccines include their easy degradability, non-integration into the host genome, and low cost.
These latest clinical advances in the use of mRNA have helped to induce anti-tumor properties for cancer treatment:
Non-formulated (naked) mRNA-based cancer vaccines
Free mRNA molecules in buffer solution are injected intradermally or intranodally such that the antigens are delivered directly to the site of T-cell activation. There are currently no active clinical trials for this. In the past 5 years, there were a few clinical trials, one of which had a 40% (2 of 5 patients) positive T-cell response for patients with melanoma.
Protamine-formulated mRNA-based cancer vaccines
Positively charged protamines complex with negatively charged mRNA to protect the molecule and form enhanced protein expression and immunogenicity. There are no active clinical trials for this therapy, however, two clinical trials have investigated the use of protamine-formulated mRNA-based cancer vaccines with limited success in the past.
mRNA-based lipoplex vaccines
Positively charged lipids complex with negatively charged mRNA to form a lipid shell and the lipoplex becomes an mRNA carrier. Many active trials are accessing the efficacy of mRNA-based lipoplex vaccines.
mRNA-based lipid nanoparticle vaccines
Comprised of ionizable lipids, cholesterol, phospholipids, and PEGylated lipids, lipid nanoparticles surround mRNA as a protective bilayer to increase circulation time. Two lipid nanoparticle mRNA cancer vaccines are currently being assessed as adjuvant therapy for patients with high-risk cutaneous melanoma.
mRNA-based dendritic cell cancer vaccines
Dendritic cell based therapeutics have been the focus for the past 30 years due to its ability to regulate the immune response and immunity. In the last 5 years, dendritic cell vaccines have been used in combination with chemotherapy or immunotherapy in cancer patients with limited success. Currently, there are 6 active clinical trials investigating mRNA-based dendritic cell vaccines in patients with glioblastoma.