Oncolytic Adenovirus: Prospects for Cancer Immunotherapy

Abstract

Immunotherapy has moved to the forefront of modern oncologic treatment in the past few decades. Various forms of immunotherapy currently are emerging, including oncolytic viruses. In this therapy, viruses are engineered to selectively propagate in tumor cells and reduce toxicity for non-neoplastic tissues. Adenovirus is one of the most frequently employed oncolytic viruses because of its capacity in tumor cell lysis and immune response stimulation. Upregulation of immunostimulatory signals induced by oncolytic adenoviruses (OAds) might significantly remove local immune suppression and amplify antitumor immune responses. Existing genetic engineering technology allows us to design OAds with increasingly better tumor tropism, selectivity, and antitumor efficacy. Several promising strategies to modify the genome of OAds have been applied: capsid modifications, small deletions in the pivotal viral genes, insertion of tumor-specific promoters, and addition of immunostimulatory transgenes. OAds armed with tumor-associated antigen (TAA) transgenes as cancer vaccines provide additional therapeutic strategies to trigger tumor-specific immunity. Furthermore, the combination of OAds and immune checkpoint inhibitors (ICIs) increases clinical benefit as evidence shown in completed and ongoing clinical trials, especially in the combination of OAds with antiprogrammed death 1/programed death ligand 1 (PD-1/PD-L1) therapy. Despite remarkable antitumor potency, oncolytic adenovirus immunotherapy is confronted with tough challenges such as antiviral immune response and obstruction of tumor microenvironment (TME). In this review, we focus on genomic modification strategies of oncolytic adenoviruses and applications of OAds in cancer immunotherapy.

Peptides-Coated Oncolytic Vaccines for Cancer Personalized Medicine

“…In this work, we have investigated PeptiCRAd, a “plug-and-play” technology based on OAd coated with tumor peptides to assess its prophylactic and therapeutic efficacy in comparison to conventional OAd encoding TAs, that currently represent one of the most exploited platforms in the field for cancer vaccines due to its immunogenicity and tumor cell lysis capability ( 33 ). PeptiCRAd consists of an OAd coated through electrostatic interactions with positively charged MHC-I restricted tumor peptides (poly-lysine tail-peptides) ( 26 ).…”

Polymeric Systems for Cancer Immunotherapy: A Review

“…It is noteworthy that the virus propagation inducing cell lysis is an extremely immunogenic process ( 157 ). This aspect is crucially relevant considering that the cancer cells usually disguise themselves from the host immune systems.…”

Smart Oncolytic Adenovirotherapy to Induce Killing of Cancer Cells and Elicit Antitumor Immunity

“…In this context, "warm" indicates that the tumor environment is infiltrated by pro-inflammatory cytokines and T cells involved in inflammation and induction of an immune response (Duan et al, 2020). The activation of the immune system leads to an antiviral response and significant antitumor responses, mainly to kill surrounding tumors and elicit antitumor immunity (Zhao et al, 2021).…”

“…Smart oncolytic adenovirotherapy can allow for targeted delivery of immunostimulatory molecules to the tumor microenvironment (Wang, Zhong, et al, 2021). This is also augmented by the potential of the virus to elicit immunity that can allow the immune system to respond efficiently to the appearance of tumor growth in another location in the body or in recurrent cancer growth (Zhao et al, 2021). CD40L serves as a very efficient immunostimulatory molecule as it is able to elicit proliferation and infiltration of helper and cytotoxic T cells and B cells while also reducing the immunosuppressive activity of the tumor by downregulating regulatory T cells (Pesonen et al, 2012).…”