Advancing personalized medicine in brain cancer: exploring the role of mRNA vaccines

Abstract

Advancing personalized medicine in brain cancer relies on innovative strategies, with mRNA vaccines emerging as a promising avenue. While the initial use of mRNA vaccines was in oncology, their stunning success in COVID-19 resulted in widespread attention, both positive and negative. Regardless of politically biased opinions, which relate more to the antigenic source than form of delivery, we feel it is important to objectively review this modality as relates to brain cancer. This class of vaccines trigger robust immune responses through MHC-I and MHC-II pathways, in both prophylactic and therapeutic settings. The mRNA platform offers advantages of rapid development, high potency, cost-effectiveness, and safety. This review provides an overview of mRNA vaccine delivery technologies, tumor antigen identification, combination therapies, and recent therapeutic outcomes, with a particular focus on brain cancer. Combinatorial approaches are vital to maximizing mRNA cancer vaccine efficacy, with ongoing clinical trials exploring combinations with adjuvants and checkpoint inhibitors and even adoptive cell therapy. Efficient delivery, neoantigen identification, preclinical studies, and clinical trial results are highlighted, underscoring mRNA vaccines' potential in advancing personalized medicine for brain cancer. Synergistic combinatorial therapies play a crucial role, emphasizing the need for continued research and collaboration in this area.

Prospects and Challenges in Developing mRNA Vaccines for Infectious Diseases and Oncogenic Viruses

“…Among the 16 patients examined, 8 showed the activation of robust immune T cells in response to the vaccines. Those individuals who demonstrated a vigorous immune response experienced extended intervals before cancer recurrence, contrasting with patients who did not exhibit an immune response to the vaccine [ 69 ]. The mRNA-4157 vaccine encodes up to 34 patient-specific neoantigens and, based on genomic sequencing, takes about six weeks to manufacture.…”

“…With no licensed vaccine or treatment currently available for Nipah virus infection, the National Institutes of Health (NIH) has initiated an early-stage clinical trial to evaluate an investigational vaccine targeting prevention. Beyond infectious diseases, extensive clinical trials are underway to explore mRNA vaccines’ efficacy against various cancers [ 69 , 73 , 74 ]. Additionally, a clinical trial has been ongoing focused on utilizing the adenine base editor (ABE) to treat sickle cell disease [ 75 ] ( Table 1 ).…”

“…LNPs are composed of auxiliary lipids, a lipid bilayer shell, polyethene glycol, cholesterol, and an aqueous core in which the mRNA vaccine is present. LNPs comprise a mixture of various lipids that confer their physical stability, unlike the liposomal complexes [ 69 , 70 ].…”

Recent Findings on Therapeutic Cancer Vaccines: An Updated Review

“…Personalized cancer vaccines are another type of immunotherapy designed to target a patient's specific cancer cells based on their unique genetic profiles to stimulate the patient's immune system to recognize and attack cancer cells more selectively [389]. Based on the different cancer vaccine platforms discussed earlier, several types of personalized cancer vaccines have been developed and used in preclinical and clinical studies, such as personalized cancer vaccines based on peptides [106,390], whole cells [390,391], nucleic acids (DNA and mRNA) [390,392], and neoantigens [390,393]. There are several steps for developing personalized cancer vaccines: (1) a genomic analysis of the patient's tumor (to identify tumor-specific characteristics, such as mutations, neoantigens, and other related characteristics that can be targeted by the immune system); (2) antigen selection (based on the genomic analysis, tumor-specific antigens are selected for inclusion in the vaccine); and (3) vaccine formulation (vaccines are formulated using different approaches, such as with peptides derived from tumor antigens, DCs loaded with tumor antigens, DNA or RNA encoding tumor antigens, neoantigens [394], or whole tumor cell lysates) [395].…”