Abstract
Oncolytic adenoviruses (OAds) are increasingly recognized as vectors for immunotherapy in the treatment of various solid tumors. The myriads of advantages of using adenovirus include targeted specificity upon infection and selective replication, which lead to localized viral burst, exponential spread of OAds, and antitumor effect. OAds can also induce a strong immune reaction due to the massive release of tumor antigens upon cytolysis and the presence of viral antigens. This review will highlight recent advances in adenoviral vectors expressing immunostimulatory effectors, such as GM-CSF (granulocyte macrophage colony-stimulating factor), interferon-α, interleukin-12, and CD40L. We will also discuss the combination of OAds with other immunotherapeutic strategies and describe the current understanding of how adenoviral vectors interact with the immune system to eliminate cancer cells.
Highlights
IntroductionResearch over the past decade has brought forth a greater understanding of tumor immunity
Research over the past decade has brought forth a greater understanding of tumor immunity.Multiple cross-talk pathways between cancer and cells of the immune system mediate in the development of a tumor microenvironment where cancer cells can evade immune detection [1].While infiltration of dendritic cells, macrophages, natural killer (NK) cells occurs early in tumor development [1,2], the pro-inflammatory actions of these cells are counteracted by immunosuppressive cells such as immature myeloid cells, regulatoryT cells, and tumor-associated macrophages [3]
With greater understanding of how adenovirus interacts with various immune cells of the tumor microenvironment, Oncolytic adenoviruses (OAds) have become an increasingly appealing and modifiable platform that can be selectively targeted to tumor cells
Summary
Research over the past decade has brought forth a greater understanding of tumor immunity. Taking advantage of CD40 overexpression in the majority of human breast cancers, the efficacy of an OAd expressing CD40L (AdEHCD40L) has been demonstrated [28] The replication of this vector is driven by a hybrid promoter with an estrogen response element (ERE) and hypoxia response element (HRE). The Hemminki group has developed a CD40L-expressing OAd vector that combines fiber modification and tumor-selective targeting [31]. Induction of tumor-antigen stimulated CD8 cells was observed even one month after CGTG-401 injection and in half the patients, a Th1 immune dominant response was seen from the presence of IFN-γ, TNF-α and IL-2 cytokines [35]. The mechanisms by which it can induce an antitumor immune response is not yet fully elucidated and necessitates further detailed analysis
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