Semliki Forest virus-based immunotherapy for cancer

ABSTRACT

Introduction: Immunotherapy has been introduced as a modern alternative for the treatment of various cancers, including the stimulation of the immune system by introduction of immunostimulatory molecules. Application of viral and non-viral vectors have provided a substantial contribution to improved delivery and expression of these immunostimulators.

Areas covered: Alphavirus vectors, based on Semliki Forest virus, have allowed immunization with self-replicating RNA, recombinant virus particles, and layered DNA/RNA vectors. The attractive features of alphaviruses comprise their broad host range and extreme RNA replication in infected cells resulting in very high recombinant protein expression levels providing enhanced immune responses and an excellent basis for immunotherapy.

Expert opinion: Immunization studies in animal tumor models have elicited strong humoral and cellular immune response, have provided prophylactic protection against tumor challenges, and have generated therapeutic efficacy in tumor-bearing animals. Clinical trials have indicated safe use of alphavirus vectors, making them attractive for cancer immunotherapy.

KEYWORDS:

• Alphavirus vectors
• cancer therapy: Clinical trials
• DNA delivery
• immunotherapy
• preclinical studies
• recombinant particles
• RNA delivery
• vaccines

Article Highlights

• Flexible self-replicating alphavirus delivery systems have been engineered for DNA, RNA and replication-deficient and -proficient alphavirus particles

• Strong humoral and cellular immune responses have been elicited in animal models

• Tumor regression has been observed in animal tumor models after administration of alphavirus vectors as DNA plasmids, RNA replicons and viral particles

• The self-replication of alphavirus RNA has confirmed that 100 to 1000-fold lower doses of DNA or RNA are required to achieve similar immune responses demonstrated for conventional DNA plasmids and synthetic RNA molecules

• Clinical trials applying alphavirus vectors have showed excellent safety profiles. However, as most studies conducted so far have been in Phase I, additional studies are required to demonstrate therapeutic efficacy.

This box summarizes key points contained in the article.

Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

One of the reviewers on this paper is a founder and stock owner of ViciniVax. All other peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.