Preclinical and clinical trials of oncolytic vaccinia virus in cancer immunotherapy:a comprehensive review

Oncolytic virotherapy has emerged as a promising treatment for human cancers owing to an ability to elicit curative effects via systemic administration.Tumor cells often create an unfavorable immunosuppressive microenvironment that degrade viral structures and impede viral replication;however,recent studies have established that viruses altered via genetic modifications can serve as effective oncolytic agents to combat hostile tumor environments.Specifically,oncolytic vaccinia virus(OVV)has gained popularity owing to its safety,potential for systemic delivery,and large gene insertion capacity.This review highlights current research on the use of engineered mutated viruses and gene-armed OVVs to reverse the tumor microenvironment and enhance antitumor activity in vitro and in vivo,and provides an overview of ongoing clinical trials and combination therapies.In addition,we discuss the potential benefits and drawbacks of OVV as a cancer therapy,and explore different perspectives in this field.

Revisiting the standards of cancer detection and therapy alongside their comparison to modern methods

In accordance with the World Health Organization data,cancer remains at the forefront of fatal diseases.An upward trend in cancer incidence and mortality has been observed globally,emphasizing that efforts in developing detection and treatment methods should continue.The diagnostic path typically begins with learning the medical history of a patient;this is followed by basic blood tests and imaging tests to indicate where cancer may be located to schedule a needle biopsy.Prompt initiation of diagnosis is crucial since delayed cancer detection entails higher costs of treatment and hospitalization.Thus,there is a need for novel cancer detection methods such as liquid biopsy,elastography,synthetic biosensors,fluorescence imaging,and reflectance confocal microscopy.Conventional therapeutic methods,although still common in clinical practice,pose many limitations and are unsatisfactory.Nowadays,there is a dynamic advancement of clinical research and the development of more precise and effective methods such as oncolytic virotherapy,exosome-based therapy,nanotechnology,dendritic cells,chimeric antigen receptors,immune checkpoint inhibitors,natural product-based therapy,tumor-treating fields,and photodynamic therapy.The present paper compares available data on conventional and modern methods of cancer detection and therapy to facilitate an understanding of this rapidly advancing field and its future directions.As evidenced,modern methods are not without drawbacks;there is still a need to develop new detection strategies and therapeutic approaches to improve sensitivity,specificity,safety,and efficacy.Nevertheless,an appropriate route has been taken,as confirmed by the approval of some modern methods by the Food and Drug Administration.

Oncolytic viruses against cancer stem cells: A promising approach for gastrointestinal cancer

Gastrointestinal cancer has been one of the five most commonly diagnosed and leading causes of cancer mortality over the past few decades. Great progress in traditional therapies has been made, which prolonged survival in patients with early cancer, yet tumor relapse and drug resistance still occurred, which is explained by the cancer stem cell(CSC) theory. Oncolytic virotherapy has attracted increasing interest in cancer because of its ability to infect and lyse CSCs. This paper reviews the basic knowledge, CSC markers and therapeutics of gastrointestinal cancer(liver, gastric, colon and pancreatic cancer), as well as research advances and possible molecular mechanisms of various oncolytic viruses against gastrointestinal CSCs. This paper also summarizes the existing obstacles to oncolytic virotherapy and proposes several alternative suggestions to overcome the therapeutic limitations.

Room for improvement in the treatment of pancreatic cancer: Novel opportunities from gene targeted therapy

Pancreatic cancer is one of the highest and in fact,unchanged mortality-associated tumor,with an exceptionally low survival rate due to its challenging diagnostic approach.So far,its treatment is based on a combination of approaches(such as surgical resection with or rarely without chemotherapeutic agents),but with finite limits.Thus,looking for additional space to improve pancreatic tumorigenesis therapeutic approach,research has focused on gene therapy with unexpectedly growing horizons not only for the treatment of inoperable pancreatic disease,but also for its early stages.In vivo gene delivery viral vectors,despite few disadvantages(possible immunogenicity,toxicity,mutagenicity,or high cost),could be one of the most efficient cancer gene therapeutic strategies for clinical application due to their superiority compared with other systems(ex vivo delivery strategies).Their dominance consists of simple preparation,easy operation and a wide range of functions.Adenoviruses are one of the most common used vectors,inducing strong immune as well as inflammatory reactions.Oncolytic virotherapy,using the above mentioned in vivo viral vectors,is one of the most promising nonpathogenic,highly-selective cytotoxic anti-cancer therapy using anti-cancer agents with high anti-tumor potency and strong oncolytic effect.There have been a variety of targeted therapeutic and pre-clinical strategies tested for gene therapy in pancreatic cancer such as gene-editing systems(e.g.,clustered regularly interspaced palindromic repeats-Cas9),RNA interference technology(e.g.,microRNAs,short hairpin RNA or small interfering RNA),adoptive immunotherapy and vaccination(e.g.,chimeric antigen receptor T-cell therapy)with encouraging results.

Recent advancements in the diagnosis and treatment of acral melanoma

Acral melanoma(AM)is the most common histologic subtype of melanoma in dark-skinned patients and is associated with a worse prognosis and a high mortality rate,largely due to the inconspicuous nature of early-stage lesions,which can lead to late diagnosis.Because of the overlapping clinical and histopathological features of AM with other forms of cutaneous melanomas,early detection of AM requires a multidisciplinary approach that integrates various diagnostic modalities,including clinical examination,dermoscopy,histopathology,molecular testing,radiological imaging,and blood tests.While surgery is the preferred method of treatment for AM,other therapeutic options may be employed based on the stage and underlying etiology of the disease.Immune checkpoint inhibitors,molecular targeted therapy,radiotherapy,chemotherapy,and oncolytic virotherapy represent promising advanced treatment options for AM.In this review,we provide an overview of the latest advancements in diagnostic and therapeutic methods for AM,highlighting the importance of early detection and the prompt,individualized management of this challenging disease.

Emerging systemic delivery strategies of oncolytic viruses:A key step toward cancer immunotherapy

Oncolytic virotherapy(OVT)is a novel type of immunotherapy that induces anti-tumor responses through selective self-replication within cancer cells and oncolytic virus(OV)-mediated immunostimulation.Notably,talimogene laherparepvec(T-Vec)developed by the Amgen company in 2015,is the first FDA-approved OV product to be administered via intratumoral injection and has been the most successful OVT treatment.However,the systemic administration of OVs still faces huge challenges,including in vivo pre-existing neutralizing antibodies and poor targeting delivery efficacy.Recently,state-of-the-art progress has been made in the development of systemic delivery of OVs,which demonstrates a promising step toward broadening the scope of cancer immunotherapy and improving the clinical efficacy of OV delivery.Herein,this review describes the general characteristics of OVs,focusing on the action mechanisms of OVs as well as the advantages and disadvantages of OVT.The emerging multiple systemic administration approaches of OVs are summarized in the past five years.In addition,the combination treatments between OVT and traditional therapies(chemotherapy,thermotherapy,immunotherapy,and radiotherapy,etc.)are highlighted.Last but not least,the future prospects and challenges of OVT are also discussed,with the aim of facilitating medical researchers to extensively apply the OVT in the cancer therapy.

Targeting gallbladder carcinoma： bone marrow-derived stem cells as therapeutic delivery vehicles of myxoma virus

Background Gallbladder carcinoma （GBC） has a high mortality rate,requiring synergistic anti-tumor management for effective treatment.The myxoma virus （MYXV） exhibits a modest clinical value through its oncolytic potential and narrow host tropism.Methods We performed viral replication assays,cell viability assays,migration assays,and xenograft tumor models to demonstrate that bone marrow-derived stem cells （BMSCs） may enhance efficiency of intravenous MYXV delivery.Results We examined the permissiveness of various GBC cell lines towards MYXV infection and found two supported single and multiple rounds of MYXV replication,leading to an oncolytic effect.Furthermore,we found that BMSCs exhibited tropism for GBC cells within a Matrigel migration system.BMSCs failed to affect the growth of GBC cells,in terms of tumor volume and survival time.Finally,we demonstrated in vivo that intravenous injection of MYXV-infected BMSCs significantly improves the oncolytic effect of MYXV alone,almost to the same extent as intratumoral injection of MYXV.Conclusion This study indicates that BMSCs are a promising novel vehicle for MYXV to clinically address gallbladder tumors.