From Conventional Therapies to Immunotherapy: Melanoma Treatment in Review

Abstract

In this review, we discuss the use of oncolytic viruses and checkpoint inhibitors in cancer immunotherapy in melanoma, with a particular focus on combinatory therapies. Oncolytic viruses are promising and novel anti-cancer agents, currently under investigation in many clinical trials both as monotherapy and in combination with other therapeutics. They have shown the ability to exhibit synergistic anticancer activity with checkpoint inhibitors, chemotherapy, radiotherapy. A coupling between oncolytic viruses and checkpoint inhibitors is a well-accepted strategy for future cancer therapies. However, eradicating advanced cancers and tailoring the immune response for complete tumor clearance is an ongoing problem. Despite current advances in cancer research, monotherapy has shown limited efficacy against solid tumors. Therefore, current improvements in virus targeting, genetic modification, enhanced immunogenicity, improved oncolytic properties and combination strategies have a potential to widen the applications of immuno-oncology (IO) in cancer treatment. Here, we summarize the strategy of combinatory therapy with an oncolytic vector to combat melanoma and highlight the need to optimize current practices and improve clinical outcomes.

Combination Therapy of Novel Oncolytic Adenovirus with Anti-PD1 Resulted in Enhanced Anti-Cancer Effect in Syngeneic Immunocompetent Melanoma Mouse Model

“…Nevertheless, metastatic melanoma responds better to immunotherapy compared to conventional chemotherapeutic drugs and radiotherapy [ 63 , 64 , 65 ]. Hence, combined treatment with novel oncolytic adenovirus and ICIs induces complementary antitumor response that could actually lead to more favorable therapeutic outcomes [ 66 , 67 , 68 , 69 ]. Indeed, pre-clinical and clinical findings show that oncolytic vectors can trigger anti-tumor immunity and increase immune cell infiltration (including cytotoxic CD8+ T cells) into the tumor microenvironment (TME).…”

“…One of the strategies to enhance the therapeutic efficacy of OVs is their use as primers for other immunotherapies. To this point, genes encoding for immunomodulatory proteins are the most commonly studied for arming oncolytic vectors and have the potential to widen the applications of immuno-oncology (IO) in cancers such as melanoma [ 69 ]. Therefore, we designed a strategy to engineer a newly oncolytic vector AdV-D24-ICOSL-CD40L and investigated its anti-tumor activity in combination with anti PD-1 in in vitro and in vivo immunocompetent mouse model engrafted with murine B16V melanoma cells.…”

Response Efficacy of PD-1 and PD-L1 Inhibitors in Clinical Trials: A Systematic Review and Meta-Analysis

“…Immune-combination therapies are often used to improve anti-tumor efficacy. In addition to the combination of chemotherapy or targeted therapy with PD-1/PD-L1 inhibitors, promising therapeutic options, such as the combination of oncolytic viruses, have shown anti-tumor activity for patients who fail to respond or achieve durable responses following immunotherapy (102)(103)(104). Oncolytic viruses are tumor specific and have the advantage of triggering anti-tumor immune responses in the tumor microenvironment, so the combination of oncolytic viruses and PD-1/PD-L1 inhibitors may be a useful strategy for future cancer treatment (102)(103)(104).…”

Advances in Targeting Cutaneous Melanoma

“…Recently, a randomized placebo-controlled study in stage III patients with CM demonstrated that adjuvant ipilimumab increases relapse-free survival (RFS) and OS. Nevertheless, more than half of patients developed severe side effects (grade 3 or 4) with ipilimumab, and five patients (1.1%) even had a grade 5 outcome [ 23 , 24 , 25 , 26 , 27 ]. As a result of ipilimumab-induced T cell activation, a variety of immune-mediated adverse effects (irAEs) have been observed, particularly including colitis, skin rashes, hepatitis, and less frequently hypophysitis.…”

“…Large, randomized investigations have demonstrated that mono-nivolumab or -pembrolizumab were superior to mono-ipilimumab. Mono-pembrolizumab in the management of naïve as well as pretreated patients resulted in sustained ORR of 30 to 40% [ 27 , 28 , 29 ]. In previously untreated CM patients, pembrolizumab revealed OS rates of 51% and 41% after three and five years, respectively.…”