Combination therapy with F5/35 fiber chimeric conditionally replicative adenoviruses expressing IL‐24 enhances the antitumor effect of temozolomide against melanoma

Abstract

BackgroundTemozolomide (TMZ) is widely used to treat melanoma; however, response rates to TMZ are low because of rapid and frequent resistance. Conditionally, replicative adenoviruses (CRAds) are an effective and promising approach. The receptor for adenovirus is coxsackie‐adenovirus receptor (CAR), which is poorly expressed in most cells. However, CD46, which is the receptor of species B adenoviruses (Ads), is highly expressed in many cells.MethodsWe constructed CRAd F5/35‐ZD55‐IL‐24, which uses the viral receptors CAR and CD46 for entry into cells. We investigated the antitumor effect of F5/35‐ZD55‐IL‐24 in combination with TMZ to treat melanoma in vitro and in vivo.ResultsThe \results indicated that F5/35‐ZD55‐IL‐24 in combination with TMZ produced additive or synergistic antitumor and pro‐apoptotic effects in melanoma cells. The combination of F5/35‐ZD55‐IL‐24 and TMZ significantly inhibited the growth of melanoma in vivo. In addition, the antitumor effect of F5/35‐ZD55‐IL‐24 was superior to that of ZD55‐IL‐24 and ZD55‐IL‐24 combined with TMZ.ConclusionsThe use of F5/35‐ZD55‐IL‐24 in conjunction with TMZ is a promising approach for anti‐melanoma therapy.Our results indicated that F5/35‐ZD55‐IL‐24 in combination with TMZ produced additive or synergistic antitumor effect and pro‐apoptotic effect in melanoma cells highly expressed CD46. The combination of F5/35‐ZD55‐IL‐24 and TMZ significantly inhibited the growth of melanoma in vivo. We also found the antitumor effect of F5/35‐ZD55‐IL‐24 was superior to ZD55‐IL‐24, the combination of F5/35‐ZD55‐IL‐24 and TMZ had a more significant antitumor effect than ZD55‐IL‐24 combining with TMZ.

Advances in engineering local drug delivery systems for cancer immunotherapy

“…Combination oncolytic virotherapy and chemotherapy has made tremendous progress in preclinical cancer models and has advanced to clinical trials (Bommareddy, Aspromonte, Zloza, Rabkin, & Kaufman, ; Simpson, Relph, Harrington, Melcher, & Pandha, ). In one example, Yang et al reported that a combination therapy consisting of an engineered adenovirus expressing IL‐24 and temozolomide induced an antitumor effect in tumor‐bearing mice (Yang et al, ). Several nanoparticle‐based local immunochemotherapy delivery strategies have been engineered to enhance treatment efficacy.…”

Absent in melanoma 2 enhances anti‐tumour effects of CAIX promotor controlled conditionally replicative adenovirus in renal cancer

“…Conditionally replicative adenoviruses (CRAds) were dependent on tumour-specific promotors by the control of virus gene (such as E1A) expression for selective replication. 1,2 The direct consequence of Ad replication results in tumour cell killing. 3 In contrast to other agents for current cancer therapies, CRAds possess the advantages of conditional selective replication viral self-spreading, highly transduction efficacy and subsequently augment anti-tumour effects in cancer cells.…”

“…16 Ads assembled with therapeutic genes can amplify the capable of lysing tumour cells selectively. 2,17 Absent in melanoma 2 (AIM2) is a member of the interferon-inducible HIN-200 protein family, and is associated with inflammation and cancer pathology. 18,19 AIM2 as a DNA sensor can form inflammasome complex by binding to cytosolic DNA and subsequently activate caspase-1 to produce IL-1β for regulating inflammatory responses.…”

“…Ads assembled with therapeutic genes can amplify the capable of lysing tumour cells selectively 2,17 . Absent in melanoma 2 (AIM2) is a member of the interferon‐inducible HIN‐200 protein family, and is associated with inflammation and cancer pathology 18,19 .…”

Clinical Significance of the Interleukin 24 mRNA Level in Head and Neck Squamous Cell Carcinoma and Its Subgroups: An In Silico Investigation

“…Some studies show that IL24 mRNA can inhibit several types of cancer cells, such as prostate cancer, kidney cancer, osteosarcoma, melanoma, colon cancer, cervical cancer, malignant glioma, breast cancer, and lung cancer, without obvious adverse effects on normal cells [ 13 ]. Recent evidence indicates that the IL24 mRNA is an underlying candidate for gene treatment of cancer through boosting apoptosis in many types of cancer cells [ 14 – 17 ]. IL24 has been reported to play vital roles in the inhibition of tumor growth and induction of tumor cell apoptosis in HNSCC cells [ 18 , 19 ].…”