Strategies for enhancing intratumoral spread of oncolytic adenoviruses

Goradel, Nasser Hashemi; Negahdari, Babak; Ghorghanlu, Sajjad; Jahangiri, Samira; Arashkia, Arash

doi:10.1016/j.pharmthera.2020.107586

Cited by 17 publications

(15 citation statements)

References 134 publications

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“…found that overexpression of matrix metalloproteinases (MMPs), MMP-1 and MMP-8, by tumor cells could increase an oncolytic HSV distribution and improve their efficacy [ 83 ]. Besides JO proteins and ECM degrading enzymes, fusogenic proteins, including Gibbon-Ape Leukemia Virus fusogenic membrane glycoprotein and fusion-associated small transmembrane (FAST) proteins, have attracted attention for enhancing the IT spread of OVs [ 84 ]. After infecting tumor cells, the IT distribution of fusogenic protein-expressing viruses is facilitated owing to the fusion between the infected and neighboring cells [ 85 ].…”

Section: Oncolytic Virotherapymentioning

confidence: 99%

A review on the advances and challenges of immunotherapy for head and neck cancer

et al. 2021

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Head and neck cancer (HNC), which includes lip and oral cavity, larynx, nasopharynx, oropharynx, and hypopharynx malignancies, is one of the most common cancers worldwide. Due to the interaction of tumor cells with immune cells in the tumor microenvironment, immunotherapy of HNCs, along with traditional treatments such as chemotherapy, radiotherapy, and surgery, has attracted much attention. Four main immunotherapy strategies in HNCs have been developed, including oncolytic viruses, monoclonal antibodies, chimeric antigen receptor T cells (CAR-T cells), and therapeutic vaccines. Oncorine (H101), an approved oncolytic adenovirus in China, is the pioneer of immunotherapy for the treatment of HNCs. Pembrolizumab and nivolumab are mAbs against PD-L1 that have been approved for recurrent and metastatic HNC patients. To date, several clinical trials using immunotherapy agents and their combination are under investigation. In this review, we summarize current the interaction of tumor cells with immune cells in the tumor microenvironment of HNCs, the main strategies that have been applied for immunotherapy of HNCs, obstacles that hinder the success of immunotherapies in patients with HNCs, as well as solutions for overcoming the challenges to enhance the response of HNCs to immunotherapies.

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Section: Oncolytic Virotherapymentioning

confidence: 99%

A review on the advances and challenges of immunotherapy for head and neck cancer

et al. 2021

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“…Tumor ECM is a barrier to access tumor cells. Co-administration of ECM-degrading enzymes such as relaxin [ 234 ], matrix metalloproteinase (MMP)-1, -8, -9 [ 131 , 226 ], chondroitinase [ 235 ], and hyaluronidase [ 226 ] with OVT, or induction of their genes expression in GLV-1h255 (VACV) and VCN-01 (OAdV) can increase OV spread into the TME and improved OVT efficiency in cancers such as retinoblastoma and pancreatic carcinoma [ 236 , 237 ]. Cellular tight junctions are also accounted as barriers for OV distribution.…”

Section: Ovt Challenges and Achievementsmentioning

confidence: 99%

“…Cellular tight junctions are also accounted as barriers for OV distribution. GMOVs can trigger the production of proteins such as penton-dodecahedra and junction opener-1, which open the cellular junction through binding to desmoglein-2 [ 226 ]. However, there are concerns about increasing the likelihood of metastasis in this method that needs further investigation.…”

Section: Ovt Challenges and Achievementsmentioning

confidence: 99%

“…However, the complexity of intratumoral injection limits dosing repetition [ 257 ]. Besides, low perfusion of OVs into dense tumors requires ECM-degradation strategies [ 226 ]. Intravenous injection is popular due to its convenience, reproducibility, and possibility to target metastatic foci [ 258 , 259 ].…”

Section: Ovt Challenges and Achievementsmentioning

confidence: 99%

“…However, it requires tumor- specific delivery systems and is more likely to cause systemic toxicity [ 257 ]. Liver tropism, physical barriers such as BBB, complement activation, and the immune system response to OV before accessing the TME are the other disadvantages of intravenous injection [ 226 , 257 ]. Intraperitoneal, intrathecal/intracranial, and intrapleural injections are suitable for targeting intra-abdominal organs, central nervous system (CNS), and lung tumors, respectively, but are limited to use in laboratory animals [ 153 ].…”

Section: Ovt Challenges and Achievementsmentioning

confidence: 99%

See 2 more Smart Citations

Oncolytic Virotherapy in Solid Tumors: The Challenges and Achievements

Jin

Liu

et al. 2021

Cancers

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Oncolytic virotherapy (OVT) is a promising approach in cancer immunotherapy. Oncolytic viruses (OVs) could be applied in cancer immunotherapy without in-depth knowledge of tumor antigens. The capability of genetic modification makes OVs exciting therapeutic tools with a high potential for manipulation. Improving efficacy, employing immunostimulatory elements, changing the immunosuppressive tumor microenvironment (TME) to inflammatory TME, optimizing their delivery system, and increasing the safety are the main areas of OVs manipulations. Recently, the reciprocal interaction of OVs and TME has become a hot topic for investigators to enhance the efficacy of OVT with less off-target adverse events. Current investigations suggest that the main application of OVT is to provoke the antitumor immune response in the TME, which synergize the effects of other immunotherapies such as immune-checkpoint blockers and adoptive cell therapy. In this review, we focused on the effects of OVs on the TME and antitumor immune responses. Furthermore, OVT challenges, including its moderate efficiency, safety concerns, and delivery strategies, along with recent achievements to overcome challenges, are thoroughly discussed.

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Erythrocyte‐Leveraged Oncolytic Virotherapy (ELeOVt): Oncolytic Virus Assembly on Erythrocyte Surface to Combat Pulmonary Metastasis and Alleviate Side Effects

Liu,

Zhang,

Huang

et al. 2023

Advanced Science

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Despite being a new promising tool for cancer therapy, intravenous delivery of oncolytic viruses (OVs) is greatly limited by poor tumor targeting, rapid clearance in the blood, severe organ toxicity, and cytokine release syndrome. Herein, a simple and efficient strategy of erythrocyte‐leveraged oncolytic virotherapy (ELeOVt) is reported, which for the first time assembled OVs on the surface of erythrocytes with up to near 100% efficiency and allowed targeted delivery of OVs to the lung after intravenous injection to achieve excellent treatment of pulmonary metastases while greatly improving the biocompatibility of OVs as a drug. Polyethyleneimine (PEI) as a bridge to assemble OVs on erythrocytes also played an important role in promoting the transfection of OVs. It is found that ELeOVt approach significantly prolonged the circulation time of OVs and increased the OVs distribution in the lung by more than tenfold, thereby significantly improving the treatment of lung metastases while reducing organ and systemic toxicity. Taken together, these findings suggest that the ELeOVt provides a biocompatible, efficient, and widely available approach to empower OVs to combat lung metastasis.

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Strategies for enhancing intratumoral spread of oncolytic adenoviruses

Cited by 17 publications

References 134 publications

A review on the advances and challenges of immunotherapy for head and neck cancer

A review on the advances and challenges of immunotherapy for head and neck cancer

Oncolytic Virotherapy in Solid Tumors: The Challenges and Achievements

Erythrocyte‐Leveraged Oncolytic Virotherapy (ELeOVt): Oncolytic Virus Assembly on Erythrocyte Surface to Combat Pulmonary Metastasis and Alleviate Side Effects

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