Non-viral platforms have until recently been applied to the delivery of mRNA encoding neoantigens. Multiple clinical trials investigating the safety and efficacy of mRNA vaccine encoding neoantigens are ongoing (TableΒ 3). Moderna and Merck collaborated to develop mRNA-5671, a Kras personalized vaccine (encoding KRAS neoantigens), alone or in together with Merckβs PD-1 specific antibody KEYTRUDA (Pembrolizumab) to treat patients with pancreatic cancer in Phase I Trial [145]. LNPs were utilized to deliver mRNA-5671 intramuscularly every 3βweeks, 9βcycles in total. Results suggested that anti-tumoral immune response was developed and the formulation is overall well-tolerated. Another product is mRNA-4157, a personalized vaccine encapsulated in LNPs, for treating patients with resected solid tumors including melanoma, bladder carcinoma and NSCLC, as monotherapy or in combination with pembrolizumab (NCT03313778). The mRNA-4157 based mono and combination therapy with pembrolizumab showed an acceptable safety profile along with remarkable neoantigen-specific T cell responses. Twelve out of thirteen patients treated by monotherapy were reported to be disease-free [148]. BioNtech collaborated with Genentech to join the campaign and to evaluate the safety and efficacy of mRNA personalized vaccine, RO7198457 delivered by Lipo-MERIT platform in multiple phase I and II clinical trials.
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