Abstract
Gene therapy with viral vectors has significantly advanced in the past few decades, with adenovirus being one of the most commonly employed vectors for cancer gene therapy. Adenovirus vectors can be divided into 2 groups: (1) replication-deficient viruses; and (2) replication-competent, oncolytic (OVs) viruses. Replication-deficient adenoviruses have been explored as vaccine carriers and gene therapy vectors. Oncolytic adenoviruses are designed to selectively target, replicate, and directly destroy cancer cells. Additionally, virus-mediated cell lysis releases tumor antigens and induces local inflammation (e.g., immunogenic cell death), which contributes significantly to the reversal of local immune suppression and development of antitumor immune responses (“cold” tumor into “hot” tumor). There is a growing body of evidence suggesting that the host immune response may provide a critical boost for the efficacy of oncolytic virotherapy. Additionally, genetic engineering of oncolytic viruses allows local expression of immune therapeutics, thereby reducing related toxicities. Therefore, the combination of oncolytic virus and immunotherapy is an attractive therapeutic strategy for cancer treatment. In this review, we focus on adenovirus-based vectors and discuss recent progress in combination therapy of adenoviruses with immunotherapy in preclinical and clinical studies.
Highlights
Cancer immunotherapy is a promising therapeutic modality for cancer which functions through stimulating the immune system to target and attack cancer cells
Another approach, using oncolytic adenovirus LOAd703 armed with immunostimulatory genes, has been reported
It is worth highlighting that arming oncolytic viruses with bispecific T cell engagers (BiTEs) realizes a combined anticancer therapy
Summary
Cancer immunotherapy is a promising therapeutic modality for cancer which functions through stimulating the immune system to target and attack cancer cells. Virotherapy is a novel and versatile form of cancer therapeutics and can be utilized as a vaccine to stimulate the immune system, as well as for direct oncolysis induced by viral replication. One of the most well-studied and promising viral vectors is adenoviruses (Ads) It can be widely used in two forms: replicative oncolytic adenoviruses and replicative deficient adenoviruses for vaccines and gene therapy [11,12]. This lytic replication cycle is favorable for oncolysis [14] when compared to enveloped viruses which complete replication by budding from intact, live, host cells In this sense, Ad-based therapy is a one of the most promising anticancer agents and has been employed for its antitumor potency via intratumoral amplification and strong oncolytic effect. We will discuss potential strategies and therapeutic effects of Ad-based therapies by combination of immunotherapeutic reagents in preclinical and clinical studies
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