Oncolytic Vaccinia Virus in Lung Cancer Vaccines

Abstract

Therapeutic cancer vaccines represent a promising therapeutic modality via the induction of long-term immune response and reduction in adverse effects by specifically targeting tumor-associated antigens. Oncolytic virus, especially vaccinia virus (VV) is a promising cancer treatment option for effective cancer immunotherapy and thus can also be utilized in cancer vaccines. Non-small cell lung cancer (NSCLC) is likely to respond to immunotherapy, such as immune checkpoint inhibitors or cancer vaccines, since it has a high tumor mutational burden. In this review, we will summarize recent applications of VV in lung cancer treatment and discuss the potential and direction of VV-based therapeutic vaccines.

Keywords: cancer vaccine; immunotherapy; non-small cell lung cancer; oncolytic virus; personalized vaccination; vaccinia virus.

Figure 3

Immunosuppressive effects of tumor microenvironment (TME). Tumor cells secrete a number of chemokines and cytokines that inhibit immune cell population, including dendritic cell (DC) and T cells. The inhibition of DC for taking up and presenting tumor antigen may cause immune ignorance. Tumor cells also recruit and generate immunosuppressive cells, such as regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and tumor-associated neutrophils, forming an immunosuppressive network that protects tumors from anti-tumor immune response, which leads to a condition called immune tolerance (modified from the presentation of Daniel W. Sharp et al. [69]).

Figure 1

Mechanism of action of therapeutic cancer vaccine. Tumor antigens from vaccines are taken up and processed by antigen-presenting cells (APCs) and presented on MHC class I and MHC class II molecules on the surface of these cells. In the tumor-draining lymph nodes, the interaction of specific T cell receptor (TCR)—the MCH-I complex—lead to the activation of CD8+ T cells and cytotoxic T lymphocytes (CTLs) and subsequently antigen recognition in the tumor cells by CTLs. CTLs then destroy the tumor cells by different processes, such as the secretion of pro-inflammatory mediators (IFNγ, TNFα) or via the perforin/granzyme pathway. The presentation of tumor antigens on MHC-II complex also leads to CD4+ T helper cell activation, which facilitates the activation of several T cell subtypes. The secretion of IL-2, IL-12, and IFN-γ by CD4+ T helper cells promotes the activation of CD8+ T cells into CTLs. In addition, activated CD4+ T helper cells promote tumor clearance by enhancing the generation of antibodies against tumor antigens by B cells, killing the activity of natural killer cells and the phagocytosis of tumor cells by macrophages Abbreviations: MHC—major histocompatibility complex; APC, IL—interleukin; IFN—interferon; NK cell—natural killer cell (re-drawn from the presentation by L. Decoster et al. [20]).

Figure 2

Mechanism of action of oncolytic virus. After the oncolytic viruses (OVs) enter normal cells, the cells stimulate different signaling pathways to limit virus spread and promote rapid cell death and the viral clearance. The virus is not able to replicate in the normal cells, leaving them unharmed. In cancer cells, OVs replicate in and lyse the cancer cells, which can directly destroy tumor cells. In addition, the release of tumor antigens and other danger signals following cell death initiates a systemic anti-tumor immune response that promotes tumor regression at distant tumor sites that are not exposed to OVs.