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Article ; Online: Nanotechnology and nano-sized tools: Newer approaches to circumvent oncolytic adenovirus limitations.

Shirazi, Maryam Mashhadi Abolghasem / Saedi, Tayebeh Azam / Moghaddam, Zahra Samadi / Nemati, Mahnaz / Shiri, Reza / Negahdari, Babak / Goradel, Nasser Hashemi

Pharmacology & therapeutics

2024 Volume 256, Page(s) 108611

Abstract: Oncolytic adenoviruses (OAds), engineered Ads preferentially infect and lyse tumor cells, have attracted remarkable attention as immunotherapy weapons for the treatment of various malignancies. Despite hopeful successes in preclinical investigations and ... ...

Abstract	Oncolytic adenoviruses (OAds), engineered Ads preferentially infect and lyse tumor cells, have attracted remarkable attention as immunotherapy weapons for the treatment of various malignancies. Despite hopeful successes in preclinical investigations and translation into clinical phases, they face some challenges that thwart their therapeutic effectiveness, including low infectivity of cancer cells, liver sequestration, pre-existing neutralizing antibodies, physical barriers to the spread of Ads, and immunosuppressive TME. Nanotechnology and nano-sized tools provide several advantages to overcome these limitations of OAds. Nano-sized tools could improve the therapeutic efficacy of OAds by enhancing infectivity and cellular uptake, targeting and protecting from pre-existing immune responses, masking and preventing liver tropism, and co-delivery with other therapeutic agents. Herein, we reviewed the constructs of various OAds and their application in clinical trials, as well as the limitations they have faced. Furthermore, we emphasized the potential applications of nanotechnology to solve the constraints of OAds to improve their anti-tumor activities.
MeSH term(s)	Humans ; Oncolytic Virotherapy ; Oncolytic Viruses ; Adenoviridae ; Neoplasms/therapy ; Nanotechnology
Language	English
Publishing date	2024-02-20
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	194735-7
ISSN	1879-016X ; 0163-7258
ISSN (online)	1879-016X
ISSN	0163-7258
DOI	10.1016/j.pharmthera.2024.108611
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Article ; Online: Heterologous administration of HPV16 E7 epitope-loaded nanocomplexes inhibits tumor growth in mouse model.

Goradel, Nasser Hashemi / Negahdari, Babak / Mohajel, Nasir / Malekshahi, Ziba Veisi / Shirazi, Maryam Mashhadi Abolghasem / Arashkia, Arash

International immunopharmacology

2021 Volume 101, Issue Pt B, Page(s) 108298

Abstract: The nanostructured complexes can result in enhanced vaccine efficacy by facilitating the distribution and uptake of antigens by antigen-presenting cells (APCs), thereby stimulating immune responses. Here, we hypothesized that either directly coating of ... ...

Abstract	The nanostructured complexes can result in enhanced vaccine efficacy by facilitating the distribution and uptake of antigens by antigen-presenting cells (APCs), thereby stimulating immune responses. Here, we hypothesized that either directly coating of nanoadjuvants including aluminum phosphate (AlPO
MeSH term(s)	Adjuvants, Immunologic/pharmacology ; Alum Compounds ; Animals ; Antigens ; CD8-Positive T-Lymphocytes/immunology ; Cancer Vaccines/immunology ; Disease Models, Animal ; Epitopes/immunology ; Immunization ; Mice ; Neoplasms ; Oligodeoxyribonucleotides ; Papillomavirus E7 Proteins ; T-Lymphocytes, Cytotoxic/immunology ; Vaccination ; Vaccine Efficacy
Chemical Substances	Adjuvants, Immunologic ; Alum Compounds ; Antigens ; CPG-oligonucleotide ; Cancer Vaccines ; Epitopes ; Oligodeoxyribonucleotides ; Papillomavirus E7 Proteins ; oncogene protein E7, Human papillomavirus type 16 ; aluminum sulfate (34S289N54E)
Language	English
Publishing date	2021-11-02
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2043785-7
ISSN	1878-1705 ; 1567-5769
ISSN (online)	1878-1705
ISSN	1567-5769
DOI	10.1016/j.intimp.2021.108298
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Article ; Online: Immunovirotherapy: The role of antibody based therapeutics combination with oncolytic viruses.

Jafari, Mahdie / Kadkhodazadeh, Maryam / Shapourabadi, Mina Bahrololoumi / Goradel, Nasser Hashemi / Shokrgozar, Mohammad Ali / Arashkia, Arash / Abdoli, Shahriyar / Sharifzadeh, Zahra

Frontiers in immunology

2022 Volume 13, Page(s) 1012806

Abstract: Despite the fact that the new drugs and targeted therapies have been approved for cancer therapy during the past 30 years, the majority of cancer types are still remain challenging to be treated. Due to the tumor heterogeneity, immune system evasion and ... ...

Abstract	Despite the fact that the new drugs and targeted therapies have been approved for cancer therapy during the past 30 years, the majority of cancer types are still remain challenging to be treated. Due to the tumor heterogeneity, immune system evasion and the complex interaction between the tumor microenvironment and immune cells, the great majority of malignancies need multimodal therapy. Unfortunately, tumors frequently develop treatment resistance, so it is important to have a variety of therapeutic choices available for the treatment of neoplastic diseases. Immunotherapy has lately shown clinical responses in malignancies with unfavorable outcomes. Oncolytic virus (OV) immunotherapy is a cancer treatment strategy that employs naturally occurring or genetically-modified viruses that multiply preferentially within cancer cells. OVs have the ability to not only induce oncolysis but also activate cells of the immune system, which in turn activates innate and adaptive anticancer responses. Despite the fact that OVs were translated into clinical trials, with T-VECs receiving FDA approval for melanoma, their use in fighting cancer faced some challenges, including off-target side effects, immune system clearance, non-specific uptake, and intratumoral spread of OVs in solid tumors. Although various strategies have been used to overcome the challenges, these strategies have not provided promising outcomes in monotherapy with OVs. In this situation, it is increasingly common to use rational combinations of immunotherapies to improve patient benefit. With the development of other aspects of cancer immunotherapy strategies, combinational therapy has been proposed to improve the anti-tumor activities of OVs. In this regard, OVs were combined with other biotherapeutic platforms, including various forms of antibodies, nanobodies, chimeric antigen receptor (CAR) T cells, and dendritic cells, to reduce the side effects of OVs and enhance their efficacy. This article reviews the promising outcomes of OVs in cancer therapy, the challenges OVs face and solutions, and their combination with other biotherapeutic agents.
MeSH term(s)	Humans ; Oncolytic Viruses ; Oncolytic Virotherapy ; Immunotherapy ; Tumor Microenvironment ; Melanoma ; Antibodies
Chemical Substances	Antibodies
Language	English
Publishing date	2022-10-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.1012806
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Article ; Online: Strategies for enhancing intratumoral spread of oncolytic adenoviruses.

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

Pharmacology & therapeutics

2020 Volume 213, Page(s) 107586

Abstract: Oncolytic viruses, effectively replicate viruses within malignant cells to lyse them without affecting normal ones, have recently shown great promise in developing therapeutic options for cancer. Adenoviruses (Ads) are one of the candidates in oncolytic ... ...

Abstract	Oncolytic viruses, effectively replicate viruses within malignant cells to lyse them without affecting normal ones, have recently shown great promise in developing therapeutic options for cancer. Adenoviruses (Ads) are one of the candidates in oncolytic virotheraoy due to its easily manipulated genomic DNA and expression of wide rane of its receptors on the various cancers. Although systematic delivery of oncolytic adenoviruses can target both primary and metastatic tumors, there are some drawbacks in the effective systematic delivery of oncolytic adenoviruses, including pre-existing antibodies and liver tropism. To overcome these limitations, intratumural (IT) administration of oncolytic viruses have been proposed. However, IT injection of Ads leaves much of the tumor mass unaffected and Ads are not able to disperse more in the tumor microenvironment (TME). To this end, various strategies have been developed to enhance the IT spread of oncolytic adenoviruses, such as using extracellular matrix degradation enzymes, junction opening peptides, and fusogenic proteins. In the present paper, we reviewed different oncolytic adenoviruses, their application in the clinical trials, and strategies for enhancing their IT spread.
MeSH term(s)	Adenoviridae/genetics ; Animals ; Humans ; Neoplasms/therapy ; Oncolytic Virotherapy/methods ; Oncolytic Viruses/genetics ; Tumor Microenvironment
Language	English
Publishing date	2020-05-30
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	194735-7
ISSN	1879-016X ; 0163-7258
ISSN (online)	1879-016X
ISSN	0163-7258
DOI	10.1016/j.pharmthera.2020.107586
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Article ; Online: Overcoming the blood-brain barrier in neurodegenerative disorders and brain tumours.

Ebrahimi, Zahra / Talaei, Sam / Aghamiri, Shahin / Goradel, Nasser Hashemi / Jafarpour, Ali / Negahdari, Babak

IET nanobiotechnology

2020 Volume 14, Issue 6, Page(s) 441–448

Abstract: Drug delivery is one of the major challenges in the treatment of central nervous system disorders. The brain needs to be protected from harmful agents, which are done by the capillary network, the so-called blood-brain barrier (BBB). This protective ... ...

Abstract	Drug delivery is one of the major challenges in the treatment of central nervous system disorders. The brain needs to be protected from harmful agents, which are done by the capillary network, the so-called blood-brain barrier (BBB). This protective guard also prevents the delivery of therapeutic agents to the brain and limits the effectiveness of treatment. For this reason, various strategies have been explored by scientists for overcoming the BBB from disruption of the BBB to targeted delivery of nanoparticles (NPs) and cells and immunotherapy. In this review, different promising brain drug delivery strategies including disruption of tight junctions in the BBB, enhanced transcellular transport by peptide-based delivery, local delivery strategies, NP delivery, and cell-based delivery have been fully discussed.
MeSH term(s)	Animals ; Blood-Brain Barrier/metabolism ; Blood-Brain Barrier/physiology ; Brain Neoplasms/drug therapy ; Brain Neoplasms/metabolism ; Cells, Cultured ; Drug Delivery Systems ; Humans ; Neurodegenerative Diseases/drug therapy ; Neurodegenerative Diseases/metabolism ; Tight Junctions/metabolism
Language	English
Publishing date	2020-07-23
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2264529-9
ISSN	1751-875X ; 1751-875X
ISSN (online)	1751-875X
ISSN	1751-875X
DOI	10.1049/iet-nbt.2019.0351
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Article ; Online: Oncolytic virotherapy: Challenges and solutions.

Goradel, Nasser Hashemi / Baker, Alexander T / Arashkia, Arash / Ebrahimi, Nasim / Ghorghanlu, Sajjad / Negahdari, Babak

Current problems in cancer

2020 Volume 45, Issue 1, Page(s) 100639

Abstract: Viruses as cancer therapies have attracted attention since the 19th century. Scientists observation that viruses can preferentially lyse cancer cells rather than healthy cells, created the field of oncolytic virology. Like other therapeutic strategies, ... ...

Abstract	Viruses as cancer therapies have attracted attention since the 19th century. Scientists observation that viruses can preferentially lyse cancer cells rather than healthy cells, created the field of oncolytic virology. Like other therapeutic strategies, oncolytic virotherapy has challenges, such as penetration into tumor bulk, anti-viral immune responses, off-target infection, adverse conditions in the tumor microenvironment, and the lack of specific predictive and therapeutic biomarkers. Whilst much progress has been made, as highlighted by the first Food and Drug Administration approval of an oncolytic virus talimogene laherparepvec (T-VEC) in 2015, addressing these issues remains a significant hurdle. Here we discuss different types of oncolytic viruses, their application in clinical trials, and finally challenges faced by the field of oncolytic virotherapy and strategies to overcome them.
MeSH term(s)	Humans ; Immunotherapy/methods ; Neoplasms/therapy ; Oncolytic Virotherapy/methods ; Oncolytic Viruses
Language	English
Publishing date	2020-08-15
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	441816-5
ISSN	1535-6345 ; 0147-0272
ISSN (online)	1535-6345
ISSN	0147-0272
DOI	10.1016/j.currproblcancer.2020.100639
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Article ; Online: Virus against virus: strategies for using adenovirus vectors in the treatment of HPV-induced cervical cancer.

Ghanaat, Momeneh / Goradel, Nasser Hashemi / Arashkia, Arash / Ebrahimi, Nasim / Ghorghanlu, Sajjad / Malekshahi, Ziba Veisi / Fattahi, Esmail / Negahdari, Babak / Kaboosi, Hami

Acta pharmacologica Sinica

2021 Volume 42, Issue 12, Page(s) 1981–1990

Abstract: Although most human papillomavirus (HPV) infections are harmless, persistent infection with high-risk types of HPV is known to be the leading cause of cervical cancer. Following the infection of the epithelium and integration into the host genome, the ... ...

Abstract	Although most human papillomavirus (HPV) infections are harmless, persistent infection with high-risk types of HPV is known to be the leading cause of cervical cancer. Following the infection of the epithelium and integration into the host genome, the oncogenic proteins E6 and E7 disrupt cell cycle control by inducing p53 and retinoblastoma (Rb) degradation. Despite the FDA approval of prophylactic vaccines, there are still issues with cervical cancer treatment; thus, many therapeutic approaches have been developed to date. Due to strong immunogenicity, a high capacity for packaging foreign DNA, safety, and the ability to infect a myriad of cells, adenoviruses have drawn attention of researchers. Adenovirus vectors have been used for different purposes, including as oncolytic agents to kill cancer cells, carrier for RNA interference to block oncoproteins expression, vaccines for eliciting immune responses, especially in cytotoxic T lymphocytes (CTLs), and gene therapy vehicles for restoring p53 and Rb function.
MeSH term(s)	Adenoviridae/genetics ; Alphapapillomavirus/pathogenicity ; Animals ; Female ; Genetic Therapy ; Genetic Vectors/therapeutic use ; Humans ; Oncolytic Virotherapy ; Papillomavirus Infections/complications ; Uterine Cervical Neoplasms/etiology ; Uterine Cervical Neoplasms/therapy ; Uterine Cervical Neoplasms/virology ; Viral Vaccines/therapeutic use
Chemical Substances	Viral Vaccines
Language	English
Publishing date	2021-02-25
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1360774-1
ISSN	1745-7254 ; 0253-9756 ; 1671-4083
ISSN (online)	1745-7254
ISSN	0253-9756 ; 1671-4083
DOI	10.1038/s41401-021-00616-5
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Article ; Online: Oncolytic virotherapy as promising immunotherapy against cancer: mechanisms of resistance to oncolytic viruses.

Goradel, Nasser Hashemi / Alizadeh, Arezoo / Hosseinzadeh, Shahnaz / Taghipour, Mitra / Ghesmati, Zeinab / Arashkia, Arash / Negahdari, Babak

Future oncology (London, England)

2021 Volume 18, Issue 2, Page(s) 245–259

Abstract: Oncolytic virotherapy has currently emerged as a powerful therapeutic approach in cancer treatment. Although the history of using viruses goes back to the early 20th century, the approval of talimogene laherparepvec (T-VEC) in 2015 increased interest in ... ...

Abstract	Oncolytic virotherapy has currently emerged as a powerful therapeutic approach in cancer treatment. Although the history of using viruses goes back to the early 20th century, the approval of talimogene laherparepvec (T-VEC) in 2015 increased interest in oncolytic viruses (OVs). OVs are multifaceted biotherapeutic agents because they replicate in and kill tumor cells and augment immune responses by releasing immunostimulatory molecules from lysed cells. Despite promising results, some limitations hinder the efficacy of oncolytic virotherapy. The delivery challenges and the upregulation of checkpoints following oncolytic virotherapy also mediate resistance to OVs by diminishing immune responses. Furthermore, the localization of receptors of viruses in the tight junctions, interferon responses, and the aberrant expression of genes involved in the cell cycle of the virus, including their infection and replication, reduce the efficacy of OVs. In this review, we present different mechanisms of resistance to OVs and strategies to overcome them.
MeSH term(s)	Biological Products/therapeutic use ; Clinical Trials as Topic ; Herpesvirus 1, Human ; Humans ; Immunotherapy/methods ; Immunotherapy/trends ; Neoplasms/immunology ; Neoplasms/therapy ; Oncolytic Virotherapy/methods ; Oncolytic Virotherapy/trends ; Oncolytic Viruses/immunology ; Treatment Outcome
Chemical Substances	Biological Products ; talimogene laherparepvec
Language	English
Publishing date	2021-11-25
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2274956-1
ISSN	1744-8301 ; 1479-6694
ISSN (online)	1744-8301
ISSN	1479-6694
DOI	10.2217/fon-2021-0802
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Article ; Online: Metabolic risk factors of ovarian cancer: a review.

Khanlarkhani, Neda / Azizi, Elham / Amidi, Fardin / Khodarahmian, Mahshad / Salehi, Ensieh / Pazhohan, Azar / Farhood, Bagher / Mortezae, Keywan / Goradel, Nasser Hashemi / Nashtaei, Maryam Shabani

JBRA assisted reproduction

2022 Volume 26, Issue 2, Page(s) 335–347

Abstract: Ovarian cancer continues to be the leading cause of death from gynecological cancers. Despite inconsistent results, patients with metabolic abnormalities, including obesity and diabetes mellitus (DM), have poorer outcomes, showing a correlation with ... ...

Abstract	Ovarian cancer continues to be the leading cause of death from gynecological cancers. Despite inconsistent results, patients with metabolic abnormalities, including obesity and diabetes mellitus (DM), have poorer outcomes, showing a correlation with ovarian cancer incidence and ovarian cancer survival. Since ovarian cancer is the most common cancer in women, and considering the increasing prevalence of obesity and DM, this paper reviews the literature regarding the relationship between the aforementioned metabolic derangements and ovarian cancer, with a focus on ovarian cancer incidence, mortality, and likely mechanisms behind them. Several systematic reviews and meta-analyses have shown that obesity is associated with a higher incidence and poorer survival in ovarian cancer. Although more studies are required to investigate the etiological relation of DM and ovarian cancer, sufficient biological evidence indicates poorer outcomes and shorter survival in DM women with ovarian cancer. A variety of pathologic factors may contribute to ovarian cancer risk, development, and survival, including altered adipokine expression, increased levels of circulating growth factors, altered levels of sex hormones, insulin resistance, hyperinsulinemia, and chronic inﬂammation. Thus, obesity and DM, as changeable risk factors, can be targeted for intervention to prevent ovarian cancer and improve its outcomes.
MeSH term(s)	Diabetes Mellitus/epidemiology ; Female ; Humans ; Incidence ; Obesity/complications ; Obesity/epidemiology ; Ovarian Neoplasms/epidemiology ; Ovarian Neoplasms/etiology ; Risk Factors
Language	English
Publishing date	2022-04-17
Publishing country	Brazil
Document type	Journal Article ; Review
ZDB-ID	2856226-4
ISSN	1518-0557 ; 1517-5693
ISSN (online)	1518-0557
ISSN	1517-5693
DOI	10.5935/1518-0557.20210067
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Article ; Online: Melatonin and cancer: From the promotion of genomic stability to use in cancer treatment.

Farhood, Bagher / Goradel, Nasser Hashemi / Mortezaee, Keywan / Khanlarkhani, Neda / Najafi, Masoud / Sahebkar, Amirhossein

Journal of cellular physiology

2018 Volume 234, Issue 5, Page(s) 5613–5627

Abstract: Cancer remains among the most challenging human diseases. Several lines of evidence suggest that carcinogenesis is a complex process that is initiated by DNA damage. Exposure to clastogenic agents such as heavy metals, ionizing radiation (IR), and ... ...

Abstract	Cancer remains among the most challenging human diseases. Several lines of evidence suggest that carcinogenesis is a complex process that is initiated by DNA damage. Exposure to clastogenic agents such as heavy metals, ionizing radiation (IR), and chemotherapy drugs may cause chronic mutations in the genomic material, leading to a phenomenon named genomic instability. Evidence suggests that genomic instability is responsible for cancer incidence after exposure to carcinogenic agents, and increases the risk of secondary cancers following treatment with radiotherapy or chemotherapy. Melatonin as the main product of the pineal gland is a promising hormone for preventing cancer and improving cancer treatment. Melatonin can directly neutralize toxic free radicals more efficiently compared with other classical antioxidants. In addition, melatonin is able to regulate the reduction/oxidation (redox) system in stress conditions. Through regulation of mitochondrial nction and inhibition of pro-oxidant enzymes, melatonin suppresses chronic oxidative stress. Moreover, melatonin potently stimulates DNA damage responses that increase the tolerance of normal tissues to toxic effect of IR and may reduce the risk of genomic instability in patients who undergo radiotherapy. Through these mechanisms, melatonin attenuates several side effects of radiotherapy and chemotherapy. Interestingly, melatonin has shown some synergistic properties with IR and chemotherapy, which is distinct from classical antioxidants that are mainly used for the alleviation of adverse events of radiotherapy and chemotherapy. In this review, we describe the anticarcinogenic effects of melatonin and also its possible application in clinical oncology.
MeSH term(s)	Animals ; Anticarcinogenic Agents/adverse effects ; Anticarcinogenic Agents/therapeutic use ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use ; Antioxidants/adverse effects ; Antioxidants/therapeutic use ; Cell Transformation, Neoplastic/drug effects ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/metabolism ; Cell Transformation, Neoplastic/pathology ; DNA Damage ; Gene Expression Regulation, Neoplastic ; Genomic Instability ; Humans ; Melatonin/adverse effects ; Melatonin/metabolism ; Melatonin/therapeutic use ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/pathology ; Neoplasms/prevention & control ; Oxidative Stress ; Signal Transduction
Chemical Substances	Anticarcinogenic Agents ; Antineoplastic Agents ; Antioxidants ; Melatonin (JL5DK93RCL)
Language	English
Publishing date	2018-09-21
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	3116-1
ISSN	1097-4652 ; 0021-9541
ISSN (online)	1097-4652
ISSN	0021-9541
DOI	10.1002/jcp.27391
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