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The investigation of oncolytic viruses in the field of cancer therapy.

Oncolytic viruses (OVs) have emerged as a potential strategy for tumor treatment due to their ability to selectively replicate in tumor cells, induce apoptosis, and stimulate immune responses. However, the therapeutic efficacy of single OVs is limited by the complexity and immunosuppressive nature of the tumor microenvironment (TME). To overcome these challenges, engineering OVs has become an important research direction. This review focuses on engineering methods and multi-modal combination therapies for OVs aimed at addressing delivery barriers, viral phagocytosis, and antiviral immunity in

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… Similarly, when oncolytic vesicular stomatitis virus serves as the carrier, miR-143 exhibits comparable antitumor effects in osteosarcoma cells ( 79 ). … Development of an oncolytic recombinant vesicular stomatitis virus encoding a tumor-suppressor microRNA . Anticancer Res . ( 2020 ) 40 : 6319–25 . doi: 10.21873/anticanres.14652 33109569 80 Jia Y Miyamoto S Soda Y Takishima Y Sagara M Liao J . …

Recent advances in oncolytic virotherapy: insights from clinical trials and combination treatment strategies.

Background and aimOncolytic virotherapy is a novel therapeutic paradigm in oncology that uses viruses to selectively replicate within cancer cells, causing targeted tumor cell destruction with minimal toxicity to healthy tissues. With the rapid growth of oncolytic virotherapy and the accumulation of clinical studies on this subject, the present review aims to provide a comprehensive evaluation of current achievements in cancer treatments involving oncolytic viruses (OVs).Main textNumerous clinical trials have been conducted to assess the therapeutic efficacy and safety of OVs across a variety

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… For example, vesicular stomatitis virus (VSV) targets cancer cells exhibiting normal PKR activity but harboring p53 deficiencies or overexpressing Ras or Myc, thereby inducing apoptosis through caspase-dependent pathways [ 27 ]. …

Immunotherapy in Multiple Myeloma.

Multiple myeloma is a complex disease and immune dysfunction has been known to play an important role in the disease pathogenesis, progression, and drug resistance. Recent efforts in drug development have been focused on immunotherapies to modify the MM disease process. Here, we summarize the emerging immunotherapies in the MM treatment landscape.

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… Vesicular Stomatitis Virus Vesicular stomatitis virus (VSV) is a potent OV agent which kills MM cells by lytic replication as well as inhibition of DNA and RNA synthesis [ 177 , 191 ]. …

Внеклеточные нуклеотиды являются посредником в вирусных инфекциях центральной нервной системы: ключи от нейроинфламмации и нейродегенерации.

Недавний рост инфекционных заболеваний, затрагивающих центральную нервную систему, вызвал обеспокоенность по поводу их роли в нейроинфламмации и нейродегенерации. Вирусные патогены или их продукты могут вторгаться в центральную нервную систему и вызывать повреждения, ведущие к менингиту, энцефалиту, менингоэнцефалиту, миелиту или постинфекционным демиелинизирующим заболеваниям. Хотя изначально нейроинфламмация имеет защитную функцию, хроническое воспаление может способствовать развитию нейродегенеративных заболеваний. Такие механизмы, как агрегация белков и клеточные расстройства, связаны с ко

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… Vesicular Stomatitis Virus Vesicular stomatitis virus (VSV) is a virus from the Rhabdoviridae family, closely related to the rabies virus, and is known to primarily affect livestock, including cattle, horses, and pigs. …

Antibody-Based Immunotherapeutic Strategies for the Treatment of Hematological Malignancies.

As the most common type of cancer in the world, hematological malignancies (HM) account for 10% of all annual cancer deaths and have attracted more attention. Conventional treatments, such as chemotherapy, radiotherapy, and hematopoietic stem cell transplantation (HSCT), could relieve patients suffering HM. However, serious side effects and high costs bring patients both physical complaints and mental pressure. Recently, compared with conventional therapeutic strategies for HM patients, antibody-based immunotherapies, including cancer vaccines, oncolytic virus therapies, monoclonal antibody tr

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… Extensive researches about OV focus on measles virus (MV), reovirus (RV), coxsackievirus (CV), and vesicular stomatitis virus (VSV) for the treatment of HM [ 17 ]. MV is a kind of negative-sense, single-strand RNA virus, which is classified as Paramyxoviridae morbillivirus. … An ongoing phase I clinical trial ( NCT03017820 ) is aimed at evaluating the tolerance and safety of vesicular stomatitis virus-interferon- β -sodium iodide symporter (VSV-IFN- β -NIS) in the treatment of MM, AML, or T cell lymphoma, which showed neurotoxicity through this trial [ 26 ]. …

Skin manifestations associated with systemic diseases - Part II.

The skin, by reflecting internal processes, externalizes what happens inside the body in many diseases. Thus, the skin, as an organ, extrapolates its functions of protection, barrier and signals the existence of systemic diseases, expanding the importance of the dermatologist beyond the skin surface. Thus, the dermatologist investigates diagnostic hypotheses for conditions related to all systems and refers patients to the appropriate specialty. Combined with examination by a trained eye, the skin, due to its easy access, is still the ideal place for performing biopsies, which often clarify the

Applications of coxsackievirus A21 in oncology.

The clinical management of cancer continues to be dominated by macroscopic surgical resection, radiotherapy, and cytotoxic drugs. The major challenge facing oncology is to achieve more selective, less toxic and effective methods of targeting disseminated tumors, a challenge oncolytic virotherapy may be well-placed to meet. Characterization of coxsackievirus A21 (CVA21) receptor-based mechanism of virus internalization and lysis in the last decade has suggested promise for CVA21 as a virotherapy against malignancies which overexpress those receptors. Preclinical studies have demonstrated proof

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… For example, vesicular stomatitis virus can reach disseminated disease after systemic delivery on irradiated vesicular stomatitis virus-infected murine colon carcinoma cells 49 and dendritic cells can “hide” reovirus from the neutralizing effects of NABs. 39 However, such ex vivo cell-based delivery …

Breaking Therapy Resistance: An Update on Oncolytic Newcastle Disease Virus for Improvements of Cancer Therapy.

Resistance to therapy is a major obstacle to cancer treatment. It may exist from the beginning, or it may develop during therapy. The review focusses on oncolytic Newcastle disease virus (NDV) as a biological agent with potential to break therapy resistance. This avian virus combines, upon inoculation into non-permissive hosts such as human, 12 described anti-neoplastic effects with 11 described immune stimulatory properties. Fifty years of clinical application of NDV give witness to the high safety profile of this biological agent. In 2015, an important milestone was achieved, namely the succ

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… In an interesting additional study, apart from the above viruses also other OVs such as measles virus, vaccinia virus , or vesicular stomatitis virus were documented to be immunogenic. … CPA has been used successfully in combination with OVs including HSV-1, adenovirus, vaccinia virus, reovirus, measles, and vesicular stomatitis virus. …

Oncolytic myxoma virus and engineering strategies for advanced cancer immunotherapy.

In cancer immunotherapy, oncolytic viruses (OVs) offer an alternative approach to kill malignant cells by inducing cancer-specific host immune system activation. Given the ongoing need for safe and effective viral vectors for immunotherapy, non-zoonotic animal viruses have attracted significant interest. Here, we review the oncolytic myxoma virus (MYXV) and emphasize its emerging role in cancer immunotherapy. We critically discuss recent advances in cancer therapy using MYXV, primarily focused on engineered viral modifications. Furthermore, we briefly review alternative delivery strategies for

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Management of herpesvirus reactivations in patients with solid tumours and hematologic malignancies: update of the Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) on herpes simplex virus type 1, herpes simplex virus type 2, and varicella zoster virus.

Clinical reactivations of herpes simplex virus or varicella zoster virus occur frequently among patients with malignancies and manifest particularly as herpes simplex stomatitis in patients with acute leukaemia treated with intensive chemotherapy and as herpes zoster in patients with lymphoma or multiple myeloma. In recent years, knowledge on reactivation rates and clinical manifestations has increased for conventional chemotherapeutics as well as for many new antineoplastic agents. This guideline summarizes current evidence on herpesvirus reactivation in patients with solid tumours and hemato

Partial impairment of cytokine responses in Tyk2-deficient mice.

To assess the role of the Janus kinase (Jak) family member Tyk2, we have generated Tyk2-/- mice. In contrast to other Jaks, where inactivation leads to a complete loss of the respective cytokine receptor signal, Tyk2-/- mice display reduced responses to IFNalpha/beta and IL-12 and a selective deficiency in Stat3 activation in these pathways. Unexpectedly, IFNgamma signaling is also impaired in Tyk2-/- mice. Tyk2-/- macrophages fail to produce nitric oxide upon lipopolysaccharide induction. Tyk2-/- mice are unable to clear vaccinia virus and show a reduced T cell response after LCMV challenge.

Регулирование пациентов с реанимированными/реферантными миеломами, лечившимися с Талкетамабом: основные моменты из точки зрения фармацевтов.

Talquetamab — семейство рецепторов с белковым белком в классе G. 5 член D (GPRC5D) и CD3-targeting bi специфическая антитела с > 71% :: общее реагирование пациентов с рецидивной или рефрактной множественной миеломой, three другие виды наркотиков. GPRC5D сильно отражается на клетках миэломы, а также некоторое выражение в обычных волосатых фолликах, коже и языке. Его уникальное выражение на этих нормальных тканях приводит к явной структуре неблагоприятных явлений (АЭ), как это было отмечено на этапе I/II. MonumenTAL-1 суд. GPRC5D-related АО включали оральные побочные эффекты (например, дисгейсия

Herpes Simplex Virus and Varicella Zoster Virus Infections in Cancer Patients.

Herpes simplex virus (HSV) and varicella zoster virus (VZV) are alpha herpesviruses that establish life-long latent infection in neuronal ganglia after primary infection. Periodic reactivation of these viruses results in recurrent infections that can have significant impact on patients' quality of life. HSV commonly causes oral and genital mucocutaneous infections whereas VZV is responsible for varicella/chickenpox and herpes zoster/shingles, but cancer patients are at particularly higher risk of complications including disseminated and visceral infections due to impaired cell-mediated immunit

Improved oncolytic and immunostimulatory activity of the spontaneous jin-3 reovirus mutant in preclinical bladder cancer models.

Immunotherapy has emerged as a promising strategy for treatment of urothelial carcinoma of the bladder (UCB) but not all patients show clinically desirable responses upon treatment with immune-checkpoint inhibition. Oncolytic viruses may unleash the full potential of immunotherapy. Besides tumor-lysing properties, oncolytic viruses can induce durable and systemic anti-viral and anti-tumor immune responses. Here, we evaluated and compared oncolytic and immunostimulatory properties of wild-type reovirus (R124) and the junction-adhesion molecule-independent mutant reovirus (jin-3) in preclinical

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… For example, T-VEC is a Food and Drug Administration (FDA)-approved herpes-simplex-virus-based therapy for advanced melanoma. 67 Other oncolytic viruses including vesicular stomatitis virus, adenovirus, and vaccinia virus have been studied in multiple cancer types, including bladder cancer. 68 , 69 , … Oncolytic vesicular stomatitis viruses are potent agents for intravesical treatment of high-risk bladder cancer Cancer Res. 68 2008 4506 4510 18559493 10.1158/0008-5472.CAN-08-0238 71 Annels N.E. Mansfield D. Arif M. Ballesteros-Merino C. Simpson G.R. Denyer M. Sandhu S.S. Melcher A.A. …

Safety and Tolerability of Letetresgene Autoleucel (GSK3377794): Pilot Studies in Patients with Advanced Non-Small Cell Lung Cancer.

PurposeThe study aims to evaluate the safety, tolerability, and antitumor response of letetresgene autoleucel (lete-cel), genetically modified autologous T cells expressing a T-cell receptor specific for New York esophageal squamous cell carcinoma 1 (NY-ESO-1)/LAGE-1a shared epitope, alone or in combination with pembrolizumab, in HLA-A*02-positive (HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06) patients with NY-ESO-1- and/or LAGE-1a-positive non-small cell lung cancer.Patients and methodsStudy 208749 was a single-arm study of lete-cel alone. Study 208471 was a multiarm study of lete-cel alone o

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… Replication-competent lentivirus (RCL) was monitored using a PCR-based assay that detects and measures copies of the gene coding for the vector’s envelope protein, vesicular stomatitis virus G protein, which is necessary for the assembly of pseudotyped infectious lentiviral particles but is absent from … Vesicular stomatitis virus G protein quantitative PCR testing was carried out on lentiviral vector, T-cell product, and PBMCs at timepoints indicated in the schedule of assessments for each study protocol. …

COVID-19 vaccination in patients with multiple myeloma: a consensus of the European Myeloma Network.

Patients with multiple myeloma frequently present with substantial immune impairment and an increased risk for infections and infection-related mortality. The risk for infection with SARS-CoV-2 virus and resulting mortality is also increased, emphasising the importance of protecting patients by vaccination. Available data in patients with multiple myeloma suggest a suboptimal anti-SARS-CoV-2 immune response, meaning a proportion of patients are unprotected. Factors associated with poor response are uncontrolled disease, immunosuppression, concomitant therapy, more lines of therapy, and CD38 an

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… Other vaccines use attenuated or inactivated SARS-CoV-2 virus (CoronaVac and BBIBP-CorV), or recombinant subunit protein (NVX-CoV2373 and ZF2001), or vesicular stomatitis virus (IIBR-100 and V590) or lentivirus (Covid-19/aAPC) as vector, or modified dendritic cells with lentivirus vectors (LV-SMENP-DC … stomatitis virus that expresses the SARS-CoV-2 spike protein) of the beta variant have been reported in young (aged 30 years; range 24–40 years) South African participants who were HIV-negative and vaccinated with the ChAdOx1 nCoV-19 vaccine. …

Advances and clinical applications of immune checkpoint inhibitors in hematological malignancies.

Immune checkpoints are differentially expressed on various immune cells to regulate immune responses in tumor microenvironment. Tumor cells can activate the immune checkpoint pathway to establish an immunosuppressive tumor microenvironment and inhibit the anti-tumor immune response, which may lead to tumor progression by evading immune surveillance. Interrupting co-inhibitory signaling pathways with immune checkpoint inhibitors (ICIs) could reinvigorate the anti-tumor immune response and promote immune-mediated eradication of tumor cells. As a milestone in tumor treatment, ICIs have been first

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… OVs are mostly utilized for research in tumor treatment in combination with ICIs, and vesicular stomatitis virus (VSV) has also been demonstrated to be effective in hematological malignancies models, such as ALL [ 109 ] and c‐HL [ 110 ] combined with ICIs. … Immunovirotherapy with vesicular stomatitis virus and PD‐L1 blockade enhances therapeutic outcome in murine acute myeloid leukemia . Blood . 2016 ; 127 ( 11 ): 1449 ‐ 58 . 26712908 10.1182/blood-2015-06-652503 PMC4797021 18 Jing Z , Wang S , Xu K , Tang Q , Li W , Zheng W , et al. …

Bortezomib in the management of multiple myeloma.

Multiple myeloma (MM) is a B-cell malignancy characterized by clonal expansion of plasma cells within the bone marrow, the presence of a serum and/or urine monoclonal protein, lytic bone lesions, and anemia. On a cellular level, the disease is characterized by complex interactions between tumor cells and the surrounding bone marrow microenvironment. Understanding of the relationship between malignant plasma cells and the microenvironment has sparked ongoing efforts to develop targeted therapeutic agents for treatment of this disease. The successful development of the first-in-class small-molec

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… Different effect of proteasome inhibition on vesicular stomatitis virus and poliovirus replication. PLoS ONE. 2008;3(4):e1887. doi: 10.1371/journal.pone.0001887. 72. Richardson P, Mitsiades C, Colson K, et al. …

Immunomodulatory and antitumor effects of type I interferons and their application in cancer therapy.

During the last decades, the pleiotropic antitumor functions exerted by type I interferons (IFNs) have become universally acknowledged, especially their role in mediating interactions between the tumor and the immune system. Indeed, type I IFNs are now appreciated as a critical component of dendritic cell (DC) driven T cell responses to cancer. Here we focus on IFN-α and IFN-β, and their antitumor effects, impact on immune responses and their use as therapeutic agents. IFN-α/β share many properties, including activation of the JAK-STAT signaling pathway and induction of a variety of cellular p

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… TLR7 also recognizes single-stranded RNA (ssRNA) derived from RNA viruses (like vesicular stomatitis virus, influenza A virus and human immunodeficiency virus) [ 237 ], synthetic poly(U) RNA and certain small interfering RNAs [ 238 ], thus pDCs are able to produce large amounts of type I IFN and cytokines … Approaches using the Vesicular Stomatitis Virus (VSV) encoding IFN-β have been shown to elicit a strong antitumor immune response, decreasing infiltrating T-reg cells and increasing CD8 + cells, and also stimulating the expression of PD-L1 on tumor cells [ 330 ]. …