Key considerations for a prostate cancer mRNA vaccine

Abstract

Prostate cancer has the second highest cancer mortality rate in the UK in males. Early prostate cancer is typically asymptomatic, with diagnosis at a locally advanced or metastatic stage. In addition, the inherent heterogeneity of prostate cancer tumours differs significantly in terms of genetic, molecular, and histological features. The successful treatment of prostate cancer is therefore exceedingly challenging. Immunotherapies, particularly therapeutic vaccines, have been widely used in preclinical and clinical studies to treat various cancers. Sipuleucel-T was the first cancer vaccine approved by the FDA for the treatment of asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC), ushering in a new era of immunotherapy. In this review, the latest immunotherapy strategies for prostate cancer are considered with key tumour-associated antigens (TAA) and tumour-specific antigens (TSA) highlighted. The key components of mRNA vaccines include in vitro transcription, stability, and immunogenicity. Finally, strategies to circumvent in vivo mRNA degradation and approaches to optimise in vitro transcription (IVT) process are also discussed.