Enadenotucirev: Difference between revisions

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'''Enadenotucirev''' is an [[investigational drug|investigational]] [[oncolytic virus]] that is in clinical trials for various cancers.<ref name="SPICE2015">{{Cite web|url=https://psioxus.com/technology-products/enadenotucirev/|title=Enadenotucirev|website=PsiOxus Therapeutics|language=en-GB|access-date=2019-07-04}}</ref>
{{Short description|Oncolytic adenovirus used in cancer therapy}}


It is an [[oncolytic]] A11/Ad3 Chimeric Group B [[Adenovirus]], previously described as '''ColoAd1'''.<ref name="EVOLVE-pos-2014">{{Cite journal|date=2019-01-28|title=A phase 1 dose escalation study of the oncolytic adenovirus enadenotucirev, administered intravenously to patients with epithelial solid tumors (EVOLVE)|journal=Journal for Immunotherapy of Cancer|volume=7|issue=1|pages=20|doi=10.1186/s40425-019-0510-7|issn=2051-1426|last1=Machiels|first1=Jean-Pascal|last2=Salazar|first2=Ramon|last3=Rottey|first3=Sylvie|last4=Duran|first4=Ignacio|last5=Dirix|first5=Luc|last6=Geboes|first6=Karen|last7=Wilkinson-Blanc|first7=Christine|last8=Pover|first8=Gillian|last9=Alvis|first9=Simon|last10=Champion|first10=Brian|last11=Fisher|first11=Kerry|last12=McElwaine-Johnn|first12=Hilary|last13=Beadle|first13=John|last14=Calvo|first14=Emiliano|pmc=6348630}}</ref>
'''Enadenotucirev''' is an [[oncolytic virus]] derived from an [[adenovirus]] that is being investigated for its potential use in [[cancer therapy]]. It is designed to selectively replicate in and destroy [[cancer cells]] while sparing normal, healthy cells. This virus is part of a broader category of [[biological therapies]] that aim to harness the body's own mechanisms to fight [[cancer]].


Enadenotucirev has also been modified with additional genes using the tumor-specific immuno-gene therapy (T-SIGn) platform to develop novel cancer gene therapy agents.
==Mechanism of Action==
Enadenotucirev is engineered to exploit the differences between cancerous and normal cells. It selectively targets and infects cancer cells due to their altered [[cellular pathways]] and [[immune evasion]] mechanisms. Once inside the cancer cell, the virus replicates, leading to cell lysis and the release of new viral particles. These particles can then infect neighboring cancer cells, amplifying the therapeutic effect. Additionally, the destruction of cancer cells by the virus can stimulate an [[immune response]] against the tumor.


The T-SIGn vectors at clinical study stage are:
==Development and Engineering==
Enadenotucirev is a chimeric virus, meaning it is created by combining genetic material from different adenovirus serotypes. This engineering enhances its ability to evade the immune system and increases its specificity for cancer cells. The virus is modified to prevent replication in normal cells, thereby reducing potential side effects.


* NG-350A: This vector contains two transgenes expressing the heavy and light chains for a secreted CD40 agonist [[monoclonal antibody]].
==Clinical Applications==
* NG-641: This vector contains four transgenes expressing secreted [[Interferon type I|Interferon alpha]], the chemokines [[CXCL9]], [[CXCL10]] and an anti-FAP/anti-CD3 bispecific T-cell activator
Enadenotucirev is being studied in various [[clinical trials]] for its efficacy against different types of cancer, including [[colorectal cancer]], [[lung cancer]], and [[ovarian cancer]]. It is often used in combination with other therapies, such as [[chemotherapy]] and [[immunotherapy]], to enhance its anti-tumor effects.


In Jan 2015 the [[European Medicines Agency]]'s (EMA) Committee for Orphan Medical Products (COMP) designated enadenotucirev as an orphan medicinal product for the treatment of [[ovarian cancer]].<ref>{{Cite web|url=https://psioxus.com/january-2015-ema-grants-positive-opinion-orphan-drug-status-ovarian-cancer-oncolytic-vaccine/|title=EMA grants positive opinion for orphan drug status for ovarian cancer oncolytic vaccine|date=2015-01-13|website=PsiOxus Therapeutics|language=en-GB|access-date=2019-07-04}}</ref>
==Advantages and Challenges==
The use of enadenotucirev offers several advantages, including its ability to selectively target cancer cells and stimulate an immune response. However, challenges remain, such as ensuring efficient delivery to tumor sites and overcoming any pre-existing immunity to adenoviruses in patients.


==Clinical trials==
==Future Directions==
Two clinical trials have been completed with enadenotucirev. The EVOLVE study <ref name="CT-octave2">[https://clinicaltrials.gov/ct2/show/NCT02028442 '''Phase I / II Study of Enadenotucirev by Sub-acute Fractionated IV Dosing in Cancer Patients (EVOLVE''')]</ref> and the MOA study.<ref name="CT-octave3">[https://clinicaltrials.gov/ct2/show/NCT02053220 '''Mechanism of Action Trial of ColoAd1 (MOA)''']</ref>
Research is ongoing to improve the delivery and efficacy of enadenotucirev. Strategies include combining it with other therapeutic agents and modifying the virus to enhance its immune-stimulating properties. The goal is to develop a robust treatment option that can be tailored to individual patients' needs.


{{as of|2019|6|df=}}, there are two active [[phase 1 trial]]s: OCTAVE (in [[ovarian cancer]])<ref name="CT-octave">[https://clinicaltrials.gov/ct2/show/NCT02028117 Phase I / II Study Of Enadenotucirev Intraperitoneally in Ovarian Cancer Patients (OCTAVE)]</ref> and SPICE (in multiple solid tumor indications) <ref name="CT-evolve2">'''[https://clinicaltrials.gov/ct2/show/NCT02636036 Phase I Study of Enadenotucirev and PD-1 Inhibitor in Subjects With Metastatic or Advanced Epithelial Tumors (SPICE)]'''</ref>
==Related Pages==
* [[Oncolytic virus]]
* [[Adenovirus]]
* [[Cancer therapy]]
* [[Immunotherapy]]


Of the T-SIGn viruses, NG-350A has an ongoing clinical study.<ref>'''[https://clinicaltrials.gov/ct2/show/NCT03852511 First in Human Study of NG-350A (an Oncolytic Adenoviral Vector Which Expresses an Anti-CD40 Antibody)]'''</ref>
[[Category:Oncolytic viruses]]
 
[[Category:Cancer treatments]]
==See also==
* [[Oncolytic adenovirus]]
** [[Oncolytic adenovirus#Directed Evolution]]
 
==References==
{{reflist}}
 
[[Category:Adenoviridae]]
[[Category:Biotechnology]]
[[Category:Experimental cancer treatments]]
[[Category:Virotherapy]]
 
 
{{oncology-stub}}
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Latest revision as of 19:17, 22 March 2025

Oncolytic adenovirus used in cancer therapy


Enadenotucirev is an oncolytic virus derived from an adenovirus that is being investigated for its potential use in cancer therapy. It is designed to selectively replicate in and destroy cancer cells while sparing normal, healthy cells. This virus is part of a broader category of biological therapies that aim to harness the body's own mechanisms to fight cancer.

Mechanism of Action[edit]

Enadenotucirev is engineered to exploit the differences between cancerous and normal cells. It selectively targets and infects cancer cells due to their altered cellular pathways and immune evasion mechanisms. Once inside the cancer cell, the virus replicates, leading to cell lysis and the release of new viral particles. These particles can then infect neighboring cancer cells, amplifying the therapeutic effect. Additionally, the destruction of cancer cells by the virus can stimulate an immune response against the tumor.

Development and Engineering[edit]

Enadenotucirev is a chimeric virus, meaning it is created by combining genetic material from different adenovirus serotypes. This engineering enhances its ability to evade the immune system and increases its specificity for cancer cells. The virus is modified to prevent replication in normal cells, thereby reducing potential side effects.

Clinical Applications[edit]

Enadenotucirev is being studied in various clinical trials for its efficacy against different types of cancer, including colorectal cancer, lung cancer, and ovarian cancer. It is often used in combination with other therapies, such as chemotherapy and immunotherapy, to enhance its anti-tumor effects.

Advantages and Challenges[edit]

The use of enadenotucirev offers several advantages, including its ability to selectively target cancer cells and stimulate an immune response. However, challenges remain, such as ensuring efficient delivery to tumor sites and overcoming any pre-existing immunity to adenoviruses in patients.

Future Directions[edit]

Research is ongoing to improve the delivery and efficacy of enadenotucirev. Strategies include combining it with other therapeutic agents and modifying the virus to enhance its immune-stimulating properties. The goal is to develop a robust treatment option that can be tailored to individual patients' needs.

Related Pages[edit]

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