Oncolytic adenovirus
[1] Of the many different viruses being explored for oncolytic potential, an adenovirus was the first to be approved by a regulatory agency, the genetically modified H101 strain.
It gained regulatory approval in 2005 from China's State Food and Drug Administration (SFDA) for the treatment of head and neck cancer.
[6] Arming with Transgenes To enhance the efficacy, therapeutic transgenes are integrated into oncolytic adenovirus[16] Immunostimulatory genes Like interferon α (IFNα),[17] tumor necrosis factor alpha (TNFα),[18] and interleukin 12 (IL-12)[19] have been integrated into oncolytic adenovirus to enhance immune response inside the tumor microenvironment.
[32] Traditional research has focussed on species C Adenovirus serotype 5 (Ad5) for creating oncolytic vaccines for the potential use as cancer treatment.
However, recent data suggests that it may not be the best virus serotype for deriving all oncolytic agents for treating human malignancies.
[34][35][36][37] The need for increased potency (infectivity and lytic activity) has led to an expanded search involving a larger number of less well studied adenovirus serotypes.
The increased biodiversity produced by the initial homologous recombination step provides a large random pool of viral candidates which can then be passed through a series of selection steps designed to lead towards a pre-specified outcome (e.g. higher tumor specific activity) without requiring any previous knowledge of the resultant viral mechanisms that are responsible for that outcome.
[38] One particular application of this approach produced ColoAd1, which is a novel Ad11p/Ad3 chimeric Group B oncolytic virus with specificity for human colon cancer and a broad spectrum of anti-cancer activity in common solid tumours.
Phase I of the trial recruited patients with metastatic solid tumors and showed evidence for virus replication within tumour sites after intravenous delivery.
Patents for the therapeutic use of ONYX-015 are held by ONYX Pharmaceuticals[49][50] and it was used in combination with the standard chemotherapeutic agents cisplatin and 5-fluorouracil to combat head and neck tumours.
[54] Further development of Onyx-015 was abandoned in the early 2000s, the exclusive rights being licensed to the Chinese company, Shanghai Sunway Biotech.
On November 17, 2005, the Chinese State Food and Drug Administration approved H101, an oncolytic adenovirus similar to Onyx-015 (E1B-55K/E3B-deleted), for use in combination with chemotherapy for the treatment of late-stage refractory nasopharyngeal cancer.
