scholarly journals The Evolution and Future of Targeted Cancer Therapy: From Nanoparticles, Oncolytic Viruses, and Oncolytic Bacteria to the Treatment of Solid Tumors

Nanomaterials ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3018
Author(s):  
Kyle M. Pierce ◽  
William R. Miklavcic ◽  
Kyle P. Cook ◽  
Mikayla Sweitzer Hennen ◽  
Kenneth W. Bayles ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Oncolytic Virus ◽  
Cancer Therapeutics ◽  
Chemotherapeutic Agents ◽  
Clinical Translation ◽  
Oncolytic Viruses ◽  
Therapeutic Drug ◽  
Common Goal ◽  
Pharmaceutical Development ◽  
Target Effects

While many classes of chemotherapeutic agents exist to treat solid tumors, few can generate a lasting response without substantial off-target toxicity despite significant scientific advancements and investments. In this review, the paths of development for nanoparticles, oncolytic viruses, and oncolytic bacteria over the last 20 years of research towards clinical translation and acceptance as novel cancer therapeutics are compared. Novel nanoparticle, oncolytic virus, and oncolytic bacteria therapies all start with a common goal of accomplishing therapeutic drug activity or delivery to a specific site while avoiding off-target effects, with overlapping methodology between all three modalities. Indeed, the degree of overlap is substantial enough that breakthroughs in one therapeutic could have considerable implications on the progression of the other two. Each oncotherapeutic modality has accomplished clinical translation, successfully overcoming the potential pitfalls promising therapeutics face. However, once studies enter clinical trials, the data all but disappears, leaving pre-clinical researchers largely in the dark. Overall, the creativity, flexibility, and innovation of these modalities for solid tumor treatments are greatly encouraging, and usher in a new age of pharmaceutical development.

scholarly journals OvirusTdb: A Repository of Oncolytic Viruses used in Cancer Treatment

2020 ◽  
Author(s):  
Anjali Lathwal ◽  
Rajesh Kumar ◽  
Gajendra P.S. Raghava
Keyword(s):  
Cancer Treatment ◽  
Cancer Cell ◽  
Oncolytic Virus ◽  
Cancer Cell Line ◽  
Chemotherapeutic Agents ◽  
Oncolytic Viruses ◽  
Virus Species ◽  
Cancer Cell Death ◽  
Anti Cancer ◽  
Fight Against Cancer

AbstractOne of the emerging technologies to fight against cancer is oncolytic virus-based immunotherapy which directly lysis tumor cells. Recently, the FDA approved an oncolytic virus named T-vec for the treatment of melanoma; several hundred other viruses are in clinical trials. In order to facilitate the scientific community to fight against cancer, we build a repository of oncolytic viruses called OvirusTdb (https://webs.iiitd.edu.in/raghava/ovirustdb/). This is a manually curated repository where information is curated from research papers and patents. The current version of the repository maintains comprehensive information on therapeutically important oncolytic viruses with 5927 records where each record has 25 fields such as the virus species, cancer cell line, synergism with anti-cancer drugs, and many more. It stores information on 09 types of DNA and 15 types of RNA viruses; 300 recombinant and 09 wildtype viral strains; tested against 124 cancer types and 427 cancer cell lines. Approximately, 1047 records show improved anti-cancer response using combinatorial approach of chemotherapeutic agents with virus strains. Nearly, 3243 and 1506 records show cancer cell death via apoptosis induction and immune activation, respectively. In summary, a user-friendly web repository of oncolytic viruses for information retrieval and analysis have been developed to facilitate researchers in designing and discovering new oncolytic viruses for effective cancer treatment.

scholarly journals Oncolytic Virus-Induced Autophagy in Glioblastoma

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3482
Author(s):  
Margarita Kamynina ◽  
Salome Tskhovrebova ◽  
Jawad Fares ◽  
Peter Timashev ◽  
Anastasia Laevskaya ◽  
...  
Keyword(s):  
Cell Death ◽  
Oncolytic Virus ◽  
Defense Mechanism ◽  
Chemotherapeutic Agents ◽  
Oncolytic Viruses ◽  
Standards Of Care ◽  
Viral Gene ◽  
Tumor Resistance ◽  
Functional Link ◽  
Cell Defense

Autophagy is a catabolic process that allows cells to scavenge damaged organelles and produces energy to maintain cellular homeostasis. It is also an effective defense method for cells, which allows them to identify an internalized pathogen and destroy it through the fusion of the autophagosome and lysosomes. Recent reports have demonstrated that various chemotherapeutic agents and viral gene therapeutic vehicles provide therapeutic advantages for patients with glioblastoma as monotherapy or in combination with standards of care. Despite nonstop efforts to develop effective antiglioma therapeutics, tumor-induced autophagy in some studies manifests tumor resistance and glioma progression. Here, we explore the functional link between autophagy regulation mediated by oncolytic viruses and discuss how intracellular interactions control autophagic signaling in glioblastoma. Autophagy induced by oncolytic viruses plays a dual role in cell death and survival. On the one hand, autophagy stimulation has mostly led to an increase in cytotoxicity mediated by the oncolytic virus, but, on the other hand, autophagy is also activated as a cell defense mechanism against intracellular pathogens and modulates antiviral activity through the induction of ER stress and unfolded protein response (UPR) signaling. Despite the fact that the moment of switch between autophagic prosurvival and prodeath modes remains to be known, in the context of oncolytic virotherapy, cytotoxic autophagy is a crucial mechanism of cancer cell death.

scholarly journals Clinical Application of Oncolytic Viruses: A Systematic Review

2020 ◽  
Vol 21 (20) ◽  
pp. 7505
Author(s):  
Mary Cook ◽  
Aman Chauhan
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Phase I ◽  
Oncolytic Virus ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Cancer Therapeutics ◽  
Oncolytic Viruses ◽  
Phase Iii ◽  
Phase Ii Trials

Leveraging the immune system to thwart cancer is not a novel strategy and has been explored via cancer vaccines and use of immunomodulators like interferons. However, it was not until the introduction of immune checkpoint inhibitors that we realized the true potential of immunotherapy in combating cancer. Oncolytic viruses are one such immunotherapeutic tool that is currently being explored in cancer therapeutics. We present the most comprehensive systematic review of all oncolytic viruses in Phase 1, 2, and 3 clinical trials published to date. We performed a systematic review of all published clinical trials indexed in PubMed that utilized oncolytic viruses. Trials were reviewed for type of oncolytic virus used, method of administration, study design, disease type, primary outcome, and relevant adverse effects. A total of 120 trials were found; 86 trials were available for our review. Included were 60 phase I trials, five phase I/II combination trials, 19 phase II trials, and two phase III clinical trials. Oncolytic viruses are feverously being evaluated in oncology with over 30 different types of oncolytic viruses being explored either as a single agent or in combination with other antitumor agents. To date, only one oncolytic virus therapy has received an FDA approval but advances in bioengineering techniques and our understanding of immunomodulation to heighten oncolytic virus replication and improve tumor kill raises optimism for its future drug development.

scholarly journals Virotherapy in Germany—Recent Activities in Virus Engineering, Preclinical Development, and Clinical Studies

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1420
Author(s):  
Dirk M. Nettelbeck ◽  
Mathias F. Leber ◽  
Jennifer Altomonte ◽  
Assia Angelova ◽  
Julia Beil ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Targeted Delivery ◽  
Viral Vector ◽  
Checkpoint Inhibitors ◽  
Therapeutic Proteins ◽  
Cancer Therapeutics ◽  
Cell Killing ◽  
Oncolytic Viruses ◽  
Preclinical Research ◽  
Research Activities

Virotherapy research involves the development, exploration, and application of oncolytic viruses that combine direct killing of cancer cells by viral infection, replication, and spread (oncolysis) with indirect killing by induction of anti-tumor immune responses. Oncolytic viruses can also be engineered to genetically deliver therapeutic proteins for direct or indirect cancer cell killing. In this review—as part of the special edition on “State-of-the-Art Viral Vector Gene Therapy in Germany”—the German community of virotherapists provides an overview of their recent research activities that cover endeavors from screening and engineering viruses as oncolytic cancer therapeutics to their clinical translation in investigator-initiated and sponsored multi-center trials. Preclinical research explores multiple viral platforms, including new isolates, serotypes, or fitness mutants, and pursues unique approaches to engineer them towards increased safety, shielded or targeted delivery, selective or enhanced replication, improved immune activation, delivery of therapeutic proteins or RNA, and redirecting antiviral immunity for cancer cell killing. Moreover, several oncolytic virus-based combination therapies are under investigation. Clinical trials in Germany explore the safety and potency of virotherapeutics based on parvo-, vaccinia, herpes, measles, reo-, adeno-, vesicular stomatitis, and coxsackie viruses, including viruses encoding therapeutic proteins or combinations with immune checkpoint inhibitors. These research advances represent exciting vantage points for future endeavors of the German virotherapy community collectively aimed at the implementation of effective virotherapeutics in clinical oncology.

scholarly journals Spatiotemporal control of CRISPR/Cas9 gene editing

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Chenya Zhuo ◽  
Jiabin Zhang ◽  
Jung-Hwan Lee ◽  
Ju Jiao ◽  
Du Cheng ◽  
...  
Keyword(s):  
Genetic Engineering ◽  
Gene Editing ◽  
Genetic Regulation ◽  
Clinical Translation ◽  
Small Molecule Activation ◽  
Simple Design ◽  
Advantages And Disadvantages ◽  
Spatiotemporal Control ◽  
Critical Challenge ◽  
Target Effects

AbstractThe clustered regularly interspaced short palindromic repeats (CRISPR)/associated protein 9 (CRISPR/Cas9) gene editing technology, as a revolutionary breakthrough in genetic engineering, offers a promising platform to improve the treatment of various genetic and infectious diseases because of its simple design and powerful ability to edit different loci simultaneously. However, failure to conduct precise gene editing in specific tissues or cells within a certain time may result in undesirable consequences, such as serious off-target effects, representing a critical challenge for the clinical translation of the technology. Recently, some emerging strategies using genetic regulation, chemical and physical strategies to regulate the activity of CRISPR/Cas9 have shown promising results in the improvement of spatiotemporal controllability. Herein, in this review, we first summarize the latest progress of these advanced strategies involving cell-specific promoters, small-molecule activation and inhibition, bioresponsive delivery carriers, and optical/thermal/ultrasonic/magnetic activation. Next, we highlight the advantages and disadvantages of various strategies and discuss their obstacles and limitations in clinical translation. Finally, we propose viewpoints on directions that can be explored to further improve the spatiotemporal operability of CRISPR/Cas9.

scholarly journals Genetic Predisposition and Chemotherapeutic Approaches Including Oncolytic Virus for the Treatment of Prostatic Adenocarcinoma

2021 ◽  
Author(s):  
Faiza Naseer ◽  
Tahir Ahmad ◽  
Kousain Kousar ◽  
Salik Kakar ◽  
Rabia Gul
Keyword(s):  
T Cells ◽  
Genetic Predisposition ◽  
Cytotoxic T Cells ◽  
Tumor Biology ◽  
Cancer Therapeutics ◽  
Chemotherapeutic Agents ◽  
Pelvic Lymphadenectomy ◽  
Prostatic Adenocarcinoma ◽  
The Body ◽  
Gnrh Analogues

Among the leading causes of cancer mortality, prostatic adenocarcinoma (PaC) is at second to lung carcinoma, but it is the most commonly happening non-cutaneous malignancy in elderly men in the world. Therapeutic options for PaC depend on age, growth & stage of malignancy, the desired outcomes and shortcomings of available treatment, estimated cost and patient compliance. Patients older than 60 years with a sluggish localized tumor may be placed on active surveillance, otherwise go with transurethral resection of the prostate (TURP), prostate artery embolization (PAE) and pelvic lymphadenectomy with/without radiation therapy. For metastatic PC androgen-deprivation therapy is an option with or without surgery. These agents decline the body’s testosterone production or block its activity by gonadotropin- releasing hormone (GnRH) analogues including leuprolide acetate and goserelin acetate implant. The hormone’s activity can be stopped by androgens antagonist such as flutamide, bicalutamide and nilutamide along with chemotherapeutic agents, such as taxanes (e.g., docetaxel, paclitaxel) but after all the disease relapses in 20-30% of patients. So, new immunological or vaccine-based therapeutic moieties have been investigated to meet the objective of providing selectivity to cancerous cells and desired therapeutic outcomes with less/no harmful effects to normal cells. The chimeric version, oncolytic poliovirus and human rhinovirus i.e. PVSRIPO is most promising feature in cancer therapeutics and activate innate immunity by neutrophils infiltration via PAMP & DAMP pathways while Sipuleucel-T expresses major histocompatibility complex (MHC) which can stimulate CD4+ helper T-cells and CD8+ cytotoxic T-cells and ultimately activate the acquired immunity against cancer cells. In this article, we have discussed the role of genetic predisposition and chemotherapeutic approaches including oncolytic poliovirus for the treatment of PaC in order to better understanding of tumor biology and mechanisms involved in chemotherapeutic drugs based resistance.

scholarly journals Applications of Nanomaterials for Theranostics of Melanoma

2020 ◽  
Vol 1 (1) ◽  
pp. 39-55
Author(s):  
Guanqiao Jin ◽  
Pohlee Cheah ◽  
Jing Qu ◽  
Lijuan Liu ◽  
Yongfeng Zhao
Keyword(s):  
Drug Delivery ◽  
Molecular Imaging ◽  
Early Diagnosis ◽  
Real Time ◽  
Treatment Plan ◽  
Chemotherapeutic Agents ◽  
The Body ◽  
Diagnostic Methods ◽  
Therapeutic Drug

Melanoma is an aggressive form of skin cancer with a very high mortality rate. Early diagnosis of the disease, the utilization of more potent pharmacological agents, and more effective drug delivery systems are essential to achieve an optimal treatment plan. The applications of nanotechnology to improve therapeutic efficacy and early diagnosis for melanoma treatment have received great interest among researchers and clinicians. In this review, we summarize the recent progress of utilizing various nanomaterials for theranostics of melanoma. The key importance of using nanomaterials for theranostics of melanoma is to improve efficacy and reduce side effects, ensuring safe implementation in clinical use. As opposed to conventional in vitro diagnostic methods, in vivo medical imaging technologies have the advantages of being a type of non-invasive, real-time monitoring. Several common nanoparticles, including ultrasmall superparamagnetic iron oxide nanoparticles, silica nanoparticles, and carbon-based nanoparticles, have been applied to deliver chemotherapeutic agents for the theranostics of melanoma. The application of nanomaterials for theranostics in molecular imaging (MRI, PET, US, OI, etc.) plays an important role in targeting drug delivery of melanoma, by monitoring the distribution site of the molecular imaging probe and the therapeutic drug in the body in real-time. Hence, it is worthwhile to anticipate the approval of these nanomaterials for theranostics in molecular imaging by the US Food and Drug Administration in clinical trials.

scholarly journals Hopf Bifurcation on a Cancer Therapy Model by Oncolytic Virus Involving the Malignancy Effect and Therapeutic Efficacy

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
F. Adi-Kusumo ◽  
L. Aryati ◽  
S. Risdayati ◽  
S. Norhidayah
Keyword(s):  
Hopf Bifurcation ◽  
Oncolytic Virus ◽  
Oncolytic Viruses ◽  
Logistic Growth ◽  
Human Immune System ◽  
Predator Prey ◽  
Predator Prey Model ◽  
Therapy Model ◽  
Human Immune ◽  
Numerical Bifurcation

We introduce a mathematical model that shows the interaction dynamics between the uninfected and the infected cancer cell populations with oncolytic viruses for the benign and the malignant cancer cases. There are two important parameters in our model that represent the malignancy level of the cancer cells and the efficacy of the therapy. The parameters play an important role to determine the possibility to have successful therapy for cancer. Our model is based on the predator-prey model with logistic growth, functional response, and the saturation effect that show the possibility for the virus to be deactivated and blocked by the human immune system after they reach a certain value. In this paper, we consider the appearance of the Hopf bifurcation on the system to characterize the treatment response based on the malignancy effect of the disease. We employ numerical bifurcation analysis when the value of the malignancy parameter is varied to understand the dynamics of the system.

Sign in / Sign up

Export Citation Format

Share Document