جستجوی مقالات مرتبط با کلیدواژه « Oncolytic viruses » در نشریات گروه « پزشکی »

Oncolytic viruses (OVs) are a promising cancer-fighting agent that has gained widespread attention due to recent advances in virology and molecular biology. These viruses selectively infect and multiply inside tumor cells, causing them to rupture and release newly synthesized viruses that stimulate the body's immune system to target the tumor cells. Clinical investigations have shown that OVs can effectively eliminate cancer cells that are resistant to traditional treatments, which is why over 100 clinical trials are currently exploring the possibility of combining them with other therapies for better efficacy. Although OVs have demonstrated enormous potential, their effectiveness in treating solid tumors is still limited. Therefore, researchers are continuously developing new viral families that can exclusively replicate in tumor cells. Currently, T-VEC is the only FDA-approved oncolytic virus, but with ongoing phase I-III clinical studies, more promising treatments are on the horizon. Furthermore, this review article provides a comprehensive overview of OVs, including their mechanism of action delivery routes, challenges in oncolytic virotherapy, current developments, the efficacy of OVs when combined with other cancer treatments, and prospects for future research.

Cancer treatment has witnessed a profound transformation in recent decades, with combination therapy emerging as a beacon of hope for patients. This review delves into the groundbreaking synergy between immunotherapy and targeted oncolytic viruses, offering a glimpse into the future of cancer conquering. Traditional methods like surgery, radiation, and chemotherapy have limitations, especially in advanced or metastatic cancers. Immunotherapy, inspired by the body's innate defenses, leverages the immune system to selectively identify and eradicate cancer cells. Immune checkpoint inhibitors, such as pembrolizumab and nivolumab, have showcased remarkable success in clinical trials, unlocking the potential of the immune system against once-intractable cancers. In tandem, oncolytic viruses exhibit precision targeting, minimizing harm to healthy tissues. Notably, herpes simplex virus type 1 (HSV-1) has proven effective against various malignancies. The fusion of immunotherapy and oncolytic viruses represents a paradigm shift in cancer treatment, harnessing the strengths of each modality. This review explores mechanisms, recent developments, clinical triumphs, and the challenges of combination therapy. The dynamic synergy of these two approaches promises to revolutionize cancer treatment, transforming it from an insurmountable foe into a manageable condition.

Non-melanoma skin cancer is a serious malignancy and white-skinned people are highly susceptible to this cancer. About 918 deaths occurred due to NMSC in the UK following the year 2018-2019. The incidence of NMSC is 18-20 times higher as compared to melanoma skin cancer. The tumor immune microenvironment of NMSC possesses a diversity of immune cells that exert pro-tumor and anti-tumor effects on the TIME. So by recognizing the tumor-promoting entities, the TIME can be remodeled. Immunotherapy provides such a treatment that activates the person’s immune system to fight against tumorigenic cells. Radiotherapy also causes the modulation of the immune system and increases the anti-tumor responses in patients. The use of immune checkpoint inhibitors after radiotherapy has produced significant survival rates in patients. Oncolytic virus therapy is a subtype of immunotherapy with a positive response in the treatment of cancer. The synthetic viral promoter is highly specific to tumor and the introduction of transgenes help them to inhibit the tumor-promoting cells and make the tumor susceptible to anti-tumor cells, thus helping the tumor to eliminate from the body. This characteristic of oncolytic virus converts the ‘‘cold TIME’’ to ‘‘hot TIME’’ which exerts a highly positive response when used ICIs. In this article, a literature review is conducted to study the role of TIME in the progression of cancer and various methods that remodel the TIME such as immunotherapy, radiotherapy, and oncolytic viruses that might help to treat NMSC.

The use of oncolytic viruses as therapeutic agents is a promising treatment for various human cancers. Several viruses have been extensively examined to achieve tumor cell death.

This study aimed at evaluating the natural oncolytic activity of mumps Hoshino vaccine strain against two human cancer cell lines, that is, HT1080 fibrosarcoma and HeLa cervical adenocarcinoma cell lines.

The cytolytic activity of the virus was evaluated using an MTT assay. Apoptosis was detected by Annexin-V/propidium iodide (PI) staining and analyzed via flow cytometry. To indicate viral replication in vivo, nude mice with HeLa heterografts were treated with the Hoshino strain of mumps virus.

It was found that human fibrosarcoma and cervical cells were more sensitive to the mumps Hoshino strain, even at a very low multiplicity of infection (MOI) compared to normal human diploid cells. The results also showed that the Hoshino strain induced apoptosis in both cancer cells. A preliminary in vivo study revealed the significant suppression of tumor growth in the group treated with the mumps Hoshino strain compared to the control group.

The Hoshino vaccine strain of mumps virus showed promising oncolytic activities against human fibrosarcoma and cervical adenocarcinoma cells.

Currently, application of oncolytic-virus in cancer treatment of clinical trials are growing. Oncolytic-reovirus is an attractive anti-cancer therapeutic agent for clinical testing. Many studies used mesenchymal stem cells (MSCs) as a carrier cell to enhance the delivery and quality of treatment with oncolytic-virotherapy. But, biosynthetic capacity and behavior of cells in response to viral infections are different. The infecting process of reoviruses takes from two-hours to one-week, depends on host cell and the duration of different stages of virus replication cycle. The latter includes the binding of virus particle, entry, uncoating, assembly and release of progeny-viruses. We evaluated the timing and infection cycle of reovirus type-3 strain Dearing (T3D), using one-step replication experiment by molecular and conventional methods in MSCs and L929 cell as control.

In this experimental study, L929 and adipose-derived MSCs were infected with different multiplicities of infection (MOI) of reovirus T3D. At different time points, the quantity of progeny viruses has been measured using virus titration assay and quantitative real-time polymerase chain reaction (qRT-PCR) to investigate the ability of these cells to support the reovirus replication. One-step growth cycle were examined by 50% cell culture infectious dose (CCID50) and qRT-PCR.

The growth curve of reovirus in cells shows that MOI: 1 might be optimal for virus production compared to higher and lower MOIs. The maximum quantity of virus production using MOI: 1 was achieved at 48-hours post-infection. The infectious virus titer became stationary at 72-hours post-infection and then gradually decreased. The virus cytopathic effect was obvious in MSCs and this cells were susceptible to reovirus infection and support the virus replication.

Our data highlights the timing schedule for reovirus replication, kinetics models and burst size. Further investigation is recommended to better understanding of the challenges and opportunities, for using MSCs loaded with reovirus in cancer-therapy.