Cancer vaccine strategies using self-replicating RNA viral platforms

Abstract

The development and success of RNA-based vaccines targeting SARS-CoV-2 has awakened new interest in utilizing RNA vaccines against cancer, particularly in the emerging use of self-replicating RNA (srRNA) viral vaccine platforms. These vaccines are based on different single-stranded RNA viruses, which encode RNA for target antigens in addition to replication genes that are capable of massively amplifying RNA messages after infection. The encoded replicase genes also stimulate innate immunity, making srRNA vectors ideal candidates for anti-tumor vaccination. In this review, we summarize different types of srRNA platforms that have emerged and review evidence for their efficacy in provoking anti-tumor immunity to different antigens. These srRNA platforms encompass the use of naked RNA, DNA-launched replicons, viral replicon particles (VRP), and most recently, synthetic srRNA replicon particles. Across these platforms, studies have demonstrated srRNA vaccine platforms to be potent inducers of anti-tumor immunity, which can be enhanced by homologous vaccine boosting and combining with chemotherapies, radiation, and immune checkpoint inhibition. As such, while this remains an active area of research, the past and present trajectory of srRNA vaccine development suggests immense potential for this platform in producing effective cancer vaccines.

Role of Biofunctionalized Nanoparticles in Digestive Cancer Vaccine Development

“…Different types of vaccines have been tested in colorectal cancer, from peptides such as carcino-embryonic antigen (CEA), melanoma-associated antigen (MAGE) or mutant neoantigens such as mutant KRAS peptide to combinations of peptide molecules of tumor-associated antigens and amputated BCG vaccine [ 44 ]. Even if in experimental studies they had antitumor effects and determined an immune response, these vaccines did not develop a significant antitumor response in phase I and II clinical trials.…”

Role of Biofunctionalized Nanoparticles in the Digestive Cancer Vaccine Development

“…Different types of vaccines have been tested in colorectal cancer, from peptides such as carcino-embryonic antigen (CEA), melanoma-associated antigen (MAGE) or mutant neoantigens such as mutant KRAS peptide to combinations of peptide molecules of tumorassociated antigens and amputated BCG vaccine [44]. Even if in experimental studies they had antitumor effects and determined an immune response, these vaccines did not develop a significant antitumor response in phase I and II clinical trials.…”

Immunotherapy for HER-2 positive breast cancer

“…Single-stranded RNA viruses are used in self-replicating vaccine platforms, including positive-stranded viruses (alphaviruses and flaviviruses) and negative-stranded viruses (measles viruses and rhabdomyoviruses) (91).Studies have shown that srRNA vaccine platforms (including those using bare RNA, DNA-emitted replicons, viral replicon particles (VRPs), and, more recently, synthetic srRNA replicon particles, are potent inducers of antitumor immunity that can be enhanced by homologous vaccine enhancement and in combination with chemotherapy, radiation, and immune checkpoint inhibition (92). Sourabh Shukla et al evaluated plant virus nanoparticle (VNP) platform technology for the treatment and prevention of HER2+ malignancies (93).…”