Historically, therapeutic cancer vaccines have demonstrated minimal efficacy. However, for the first time, an anti-cancer vaccine has shown significant promise in a clinical trial. The combination therapy of Moderna’s mRNA vaccine “mRNA-4157/V940” in combination with Merck & Co’s anti-PD-1 therapy “Keytruda”  has reportedly cut the risk of melanoma recurrence or death by 44% compared to Keytruda monotherapy. This will revitalize the field of therapeutic cancer vaccines, opines GlobalData, a leading data and analytics company.

Avigayil Chalk, PhD, Oncology & Hematology Analyst at GlobalData, comments: “mRNA-4157/V940 differs from the previously trialled anti-cancer vaccines, and can be described as a personalized therapeutic. The vaccine contains a single mRNA molecule encoding up to 34 tumor-specific antigens, which are selected based on the patient’s individual tumor mutations. Once administered, the mRNA is translated,  and the resultant peptides are processed and presented to the immune system, thereby stimulating an anti-tumor immune response.”

Keytruda was the first anti-PD-1 therapy to receive regulatory approval for the treatment of advanced melanoma. The anti-PD-1 monoclonal antibody (mAb) is an immunce checkpoint inhibitor (ICI) and works by blocking the inhibitory interaction between the PD-1 receptor found on T-cells and PD-L1/PD-L2, which is expressed on tumor cells. This leads to activation and proliferation of T-cells, which can generate a potent anti-tumor immune response. ICIs can produce very durable reposnes in patients, even curing advanced disease in a subset of patients.

Chalk continues: “While Keytruda and other immunotherapy drugs have revolutionized the outlook for patients with melanoma, a significant proportion of patients still fail to respond to therapy, or experience disease relapse. A combination of Keytruda with mRNA-4157/V940 primes the ‘unleashed’ immune system against tumors expressing the neoantigens incorporated in the mRNA vaccine.”

While mRNA-4157/V940 is the first anti-cancer vaccine to demonstrate such promising efficacy, there are multiple mRNA vaccines currently in development for a range of oncology indications.

GlobalData’s research reveals that melanoma has more mRNA vaccines in its pipeline than any other cancer type, with several agents already in clinical trials, including BioNTech’s BNT-111 and Genentech and BioNTech’s BNT-122. In contrast to mRNA-4157/V940, BNT-111 is an “off-the-shelf” mRNA vaccine that encodes just four melanoma-associated antigens that are found in 90% of cutaneous melanomas.

Chalk concludes: “The use of mRNA vaccines for the treatment of cancer has become a promising approach, particularly when combined with ICIs to enable a more ferocious anti-tumor immune response. It remains to be seen whether a personalized therapy such as mRNA-4157/V940 is required for maximum efficacy, or whether an ‘off-the-shelf’ product can demonstrate equivalent efficacy. Personalized mRNA vaccines are likely to come with a hefty price tag and a relatively long manufacturing process, which will act as barriers to their therapeutic uptake.”