intismeran autogene (mRNA-4157)

Clinical data reflects this, with the mRNA vaccine mRNA-4157 (KEYNOTE-942) demonstrating a significant recurrence-free survival (RFS) benefit in the adjuvant setting...This reflects the logistical and biological complexities inherent in developing personalised vaccines, highlighting challenges in both manufacturing and subject recruitment. These remain key obstacles impeding the widespread clinical application of such vaccines.

P2, N=180, Recruiting, Merck Sharp & Dohme LLC | N=59 --> 180

P3, N=876, Not yet recruiting, Merck Sharp & Dohme LLC

P2, N=59, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

P2, N=180, Recruiting, Merck Sharp & Dohme LLC | N=49 --> 180

P2, N=49, Recruiting, Merck Sharp & Dohme LLC | N=15 --> 49

P2/3, N=46, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

P1/2, N=15, Not yet recruiting, Merck Sharp & Dohme LLC

P1, N=161, Active, not recruiting, ModernaTX, Inc. | N=242 --> 161 | Trial completion date: Aug 2027 --> Nov 2027 | Trial primary completion date: Aug 2027 --> Nov 2027

Nanovaccine platforms can potentially overcome some constraints of conventional vaccines by enhancing lymph node targeting, antigen stability, and immunogenicity. Further research in this field could further advance targeted cancer immunotherapy.

This review synthesizes recent advances in biomimetic and personalized nanovaccine design, highlighting clinical progress in lipid nanoparticle (LNP)-based vaccines such as BNT111 and mRNA-4157, emerging innate immune adjuvants including Toll-like receptor (TLR) and stimulator of interferon genes (STING) agonists, and rational combination strategies with immune checkpoint blockade. Key safety and quality consideration including immunotoxicity, off-target immune activation, and batch heterogeneity are critically evaluated alongside emerging engineering solutions. Finally, future directions integrating AI-guided neoantigen prediction, modular microfluidic manufacturing, and multi-omic biomarker frameworks are discussed to accelerate next generation cancer nanovaccine translation.

Most trials focused on Stage III/IV patients (91.1%): key trials showed mRNA-4157 + pembrolizumab reduced recurrence/death risk by 49% in resected melanoma, and herpes simplex virus RP1 + nivolumab achieved 58.3% objective response rate (ORR) in ICI-resistant patients. However, challenges include tumor heterogeneity, immunosuppressive tumor microenvironment (TME), inefficient delivery, geographical R&D imbalance, and low Phase III conversion. Interdisciplinary collaboration, international multicenter trials, optimized clinical design (e.g., early-stage patient enrollment), and policy support are needed to advance their clinical translation.