Naturally occurring oncolytic viruses, which replicate in tumour cells and trigger apoptosis and immune responses while sparing healthy cells, were first discovered at the turn of the 19th century. The resulting interest in their use as cancer therapeutics is based on observations that some cancer patients with viral infections go into remission for a brief time. Research into this approach has been ongoing for over a century, with the first clinical trial of a hepatitis virus in Hodgkin’s disease in 1949, but oncolytic viruses did not reach the market until 2004 in Latvia and 2005 in China. [1-4]
The oncolytic viruses market is predicted to be worth around $399 billion by 2035, at a compound annual growth rate (CAGR) of 25.55% [5]
An introduction to oncolytic viruses
The mechanism of action of oncolytic viruses is complex and includes direct lysis of tumour cells, inducing tumour-specific T cell responses. They also have potential to bypass tumour immune evasion, which could mean lower levels of treatment resistance. Because the mechanism of action doesn’t generally overlap with that of other cancer therapies, they could be used in combination with existing and new treatments. [1-4]
Oncolytic viruses can be RNA or DNA viruses. Naturally occurring oncolytic viruses include reovirus, Newcastle disease virus, myxoma virus, picornavirus and Seneca valley virus. Genetic engineering has made it possible for researchers to boost the in vivo and antitumour immune response to the viruses, improve their replication efficiency within cancer cells, increase safety and enhance their targeting. Viruses used in a genetically engineered form include measles virus, poliovirus, vaccinia virus, adenovirus and herpes simplex virus. [2, 6]
A number of unmodified and genetically engineered oncolytic viruses have received market approval: [3, 7]
· Rigvir (ECHO-7; Picornavirus)
o Approved in 2004 in Latvia for melanoma (unmodified virus)
· Oncorine (H101; Adenovirus serotype 5)
o Shanghai Sunway Biotech: Approved in 2005 in China for head and neck cancer (genetically modified)
· Imlygic (T-VEC, talimogene laherparepvec; HSV-1)
o Amgen: Approved in 2015 in the US and Europe for metastatic melanoma (genetically modified)
· DELYTACT (teserpaturev/G47Δ; HSV-1)
o Daiichi Sankyo: Approved in 2021 in Japan for primary brain cancer (genetically modified)
The oncolytic viruses pipeline
A selection of products in development includes: [7-12]
· Adlai Nortye Biopharma
o Pelareorep (naturally occurring dsRNA reovirus) in Phase III trials in breast cancer
· BioInvent/Transgene
o BT-001 (oncolytic virus + anti-CTLA4 antibody) in a Phase I/IIa trial alone and in combination in solid tumours
· Candel Therapeutics
o CAN-2409 (engineered adenovirus) in Phase III trials in prostate cancer
· CG Oncology/Kissei Pharmaceutical
o Cretostimogene grenadenorepvec (engineered adenovirus) in Phase III trials in bladder cancer
· DNAtrix
o DNX-2401 (engineered adenovirus) in a Phase II trial in glioblastoma multiforme
· EpicentRx [9]
o AdAPT-001 (engineered adenovirus) in Phase II trials alone and in combination in sarcoma
· Genelux [7]
o Olvimulogene nanivacirepvec (engineered vaccinia virus) in Phase III trials in fallopian tube, ovarian and peritoneal cancer
· Lokon Pharma
o LOAd 703 (engineered adenovirus) in Phase II trials in pancreatic cancer, ovarian cancer, colorectal cancer and malignant melanoma
· Oncolys Biopharma
o Telomelysin (OBP-301; engineered adenovirus) in Phase II trials in adenocarcinoma, gastric cancer, head and neck cancer and oesophageal cancer
· Replimune
o RP1 (vusolimogene oderparepvec; en...
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