Viral Vector-Based Therapeutic Cancer Vaccines

Abstract

Most viruses are naturally immunogenic and can be engineered to express tumor antigen transgenes. Moreover, many types of recombinant viruses have been shown to infect professional antigen-presenting cells, specifically dendritic cells, and express their transgenes. This enhanced presentation of tumor antigens to the immune system has led to an increase in the frequency and avidity of cytotoxic T-lymphocytes that target tumor cells expressing the tumor antigen(s) encoded in the vaccine vector. Logistically, recombinant viruses can be produced, administered and quality controlled more easily compared to other immunotherapy strategies. The intrinsic properties of each virus have distinct advantages and disadvantages, which can determine their applicability in a particular therapeutic setting. The disadvantage of some vectors is the development of host-induced neutralizing antibodies to the vector itself, thus limiting its continued use. The “off-the-shelf” nature of viral vaccine platforms renders them exceptionally suitable for multicenter randomized trials. This review will describe and discuss the strategies employed and results using viral-based vaccines, with emphasis on phase II and III clinical trials. Future directions will involve the evaluation of viral-based vaccines in the adjuvant and neo-adjuvant settings, in patients with low burden metastatic disease, and in combination with other forms of therapy including immunotherapy.

Delivery of viral-vectored vaccines by B cells represents a novel strategy to accelerate CD8+ T-cell recall responses

“…In particular, viral vectors are being widely studied for use in gene-based vaccine strategies because of their ability to deliver antigens into the antigen-processing pathways needed to stimulate major histocompatibility complex (MHC) class Irestricted CTL responses. 1,2 Furthermore, the frequency of transgene-specific T cells can be further increased by combining recombinant viral vectors in heterologous prime-boost regimens. 3,4 A central role for dendritic cells (DCs) in priming CD8 1 T cells has been well-established following viral infection or vaccination.…”

“…1,2 Furthermore, the frequency of transgene-specific T cells can be further increased by combining recombinant viral vectors in heterologous prime-boost regimens. 3,4 A central role for dendritic cells (DCs) in priming CD8 1 T cells has been well-established following viral infection or vaccination. 5,6 This includes the transportation of viral antigens by migratory DCs to draining lymph nodes or spleen and subsequent antigen presentation by lymphoid residential DCs.…”

Semliki Forest virus biodistribution in tumor-free and 4T1 mammary tumor-bearing mice: a comparison of transgene delivery by recombinant virus particles and naked RNA replicon

“…1,2 Among other recombinant viruses, alphaviral vectors are efficient mammalian expression systems, allowing transient high-level transgene expression and rapid high-titer recombinant particle production. 3,4 These vectors are promising in the field of cancer gene therapy because of their strong cytopathic effects through the induction of p53-independent apoptosis, 5,6 their ability to efficiently overcome immunological tolerance by the activation of innate antiviral pathways 7,8 and the subsequent triggering of the cytotoxic T-lymphocyte response against tumors.…”

Immunotherapy in Colorectal Cancer

“…Many types of recombinant viruses are naturally immunogenic, infect APCs (specifically DCs), and express TAAs [76] . The natural immunogenicity of viral vectors acts as an adjuvant to help boost TAA-specific immune responses.…”