Cancer/Testis Antigens as Targets for RNA-Based Anticancer Therapy

Abstract

In the last few decades, RNA-based drugs have emerged as a promising candidate in the treatment of various diseases. The introduction of messenger RNA (mRNA) as a vaccine or therapeutic agent enables the production of almost any functional protein/peptide. The key to applying RNA therapy in clinical trials is developing safe and effective delivery systems. Exosomes and lipid nanoparticles (LNPs) have been exploited as promising vehicles for drug delivery. This review discusses the feasibility of exosomes and LNPs as vehicles for mRNA delivery. Cancer/testis antigens (CTAs) show restricted expression in normal tissues and widespread expression in cancer tissues. Many of these CTAs show expression in the sera of patients with cancers. These characteristics of CTAs make them excellent targets for cancer immunotherapy. This review summarizes the roles of CTAs in various life processes and current studies on mRNAs encoding CTAs. Clinical studies present the beneficial effects of mRNAs encoding CTAs in patients with cancers. This review highlight clinical studies employing mRNA-LNPs encoding CTAs.

Cancer testis antigens: Emerging therapeutic targets leveraging genomic instability in cancer

“…Cancer-testis antigens (CTA) are a large family of tumor-associated proteins that under physiological conditions are predominantly expressed in the testes, specifically in the proliferating germ cells, spermatogonia and spermatocytes. 1 , 2 , 3 , 4 , 5 , 6 , 7 Their expression is tightly controlled by DNA methylation and histone modifications involving epigenetic modulatory proteins such as the germ-cell specific CCCTC-binding factor (CTCF) and Brother of Regulator of Imprinted Sites (BORIS). 4 , 8 , 9 , 10 , 11 Furthermore, aberrant expression of CTAs in tumors may depend on chromosomal location since chromosome X-encoded CTAs, encompassing the majority of multigene CTA families (MAGE/GAGE/PAGE/XAGE, NY-ESO-1 and SSX genes), are more frequently expressed in tumors compared to autosomal single-copy CTA genes (non-CT-X).…”

“… 22 , 23 , 24 , 25 , 26 Traditionally, CTAs are thought to predominantly support cancer hallmarks such as sustaining proliferative signaling, resisting cell death, deregulating cellular energetics, activating invasion and metastasis, inducing angiogenesis, and genome instability and mutation. 5 , 6 , 7 , 8 , 12 , 27 , 28 For instance, members of the MAGE family have been shown to, in part through binding of the master tumor suppressor p53, promote tumor cell proliferation and cell cycle progression while inhibiting tumor cell survival. 29 , 30 SSX and CAGE family members increase tumor cell growth and survival through the activation of the MAPK and Wnt signaling pathways and upregulation of cell cycle proteins.…”