The dl1520 virus is found preferentially in tumor tissue after direct intratumoral injection in oral carcinoma.
OBJECTIVE
dl1520 (also known as Onyx-015) is an E1B-deleted adenovirus designed to selectively lyse p53-deficient cancer cells. Clinical trials involving patients with recurrent squamous cell carcinoma of the head and neck have shown clinical efficacy, but no direct evidence as to the tumor or p53 selectivity of the virus was demonstrated. We wanted to determine whether dl1520 is selective for survival and replication within tumor tissue after direct injection and whether this is determined by p53 status of the tissues. We also wanted to ascertain whether the virus has any macroscopic effect on normal tissue.


METHODS
An open-label Phase II trial was devised in which a fixed dose of the virus was administered to 15 patients via a direct intertumoral injection before surgery for untreated oral squamous cell carcinoma. The agent was also delivered into an area of adjacent normal buccal mucosa. Specimens of the excised tumor and of biopsies of the injected normal tissue were assessed for viral presence and p53 status.


RESULTS
We demonstrated that the virus replicates selectively in tumor as opposed to normal tissue after this direct injection. It was not possible to determine whether this selectivity was p53 related. It was found that dl1520 triggers an early rise in apoptosis levels in injected normal tissues. No adverse effects of viral injection were noted.


CONCLUSIONS
This is the first report of injection of dl1520 into previously untreated squamous cell cancer. The data support the concept that dl1520 is replication deficient in normal, compared with cancerous, tissues and has potential as a selective anticancer agent against tumor tissues.
Morley
Stephen
S
Department of Plastic Surgery, Wythenshawe Hospital, Manchester, UK. Stephen.morley7@ntlworld.com
MacDonald
Gordon
G
Kirn
David
D
Kaye
Stan
S
Brown
Robert
R
Soutar
David
D
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002277:Carcinoma / Q000628:therapy* / Q000821:virology*; D016923:Cell Death; D002470:Cell Survival; D002986:Clinical Trials as Topic; D004279:DNA, Viral / Q000032:analysis* / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000628:therapy* / Q000821:virology*; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism; D013696:Temperature; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014765:Viral Vaccines
D000970:Antineoplastic Agents; D004279:DNA, Viral; D016159:Tumor Suppressor Protein p53; D014765:Viral Vaccines; C464532:dl1520