Selective replication and oncolysis in p53 mutant tumors with ONYX-015, an E1B-55kD gene-deleted adenovirus, in patients with advanced head and neck cancer: a phase II trial
- PMID: 11103798
Selective replication and oncolysis in p53 mutant tumors with ONYX-015, an E1B-55kD gene-deleted adenovirus, in patients with advanced head and neck cancer: a phase II trial
Abstract
ONYX-015 is an E1B-55kDa gene-deleted adenovirus engineered to selectively replicate in and lyse p53-deficient cancer cells. To evaluate the selectivity of ONYX-015 replication and cytopathic effects for the first time in humans, we carried out a Phase II clinical testing of intratumoral and peritumoral ONYX-015 injection in 37 patients with recurrent head and neck carcinoma. Patients received ONYX-015 at a daily dose of 1 x 10(10) plaque-forming units (pfu) via intratumoral injection for 5 days during week 1 of each 3-week cycle (n = 30; cohort A), or 1 x 10(10) pfu twice a day for 10 days during weeks 1 and 2 of each 3-week cycle. Posttreatment biopsies documented selective ONYX-015 presence and/or replication in the tumor tissue of 7 of 11 patients biopsied on days 5-14, but not in immediately adjacent normal tissue (0 of 11 patients; P = 0.01). Tissue destruction was also highly selective; significant tumor regression (>50%) occurred in 21% of evaluable patients, whereas no toxicity to injected normal peritumoral tissues was demonstrated. p53 mutant tumors were significantly more likely to undergo ONYX-015-induced necrosis (7 of 12) than were p53 wild-type tumors (0 of 7; P = 0.017). High neutralizing antibody titers did not prevent infection and/or replication within tumors. ONYX-015 is the first genetically engineered replication-competent virus to demonstrate selective intratumoral replication and necrosis in patients. This agent demonstrates the promise of replication-selective viruses as a novel therapeutic platform against cancer.
Similar articles
-
A phase I study of Onyx-015, an E1B attenuated adenovirus, administered intratumorally to patients with recurrent head and neck cancer.Clin Cancer Res. 2000 Mar;6(3):798-806. Clin Cancer Res. 2000. PMID: 10741699 Clinical Trial.
-
a controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer.Nat Med. 2000 Aug;6(8):879-85. doi: 10.1038/78638. Nat Med. 2000. PMID: 10932224 Clinical Trial.
-
Safety and feasibility of injection with an E1B-55 kDa gene-deleted, replication-selective adenovirus (ONYX-015) into primary carcinomas of the pancreas: a phase I trial.Gene Ther. 2001 Feb;8(4):308-15. doi: 10.1038/sj.gt.3301398. Gene Ther. 2001. PMID: 11313805 Clinical Trial.
-
Clinical research results with dl1520 (Onyx-015), a replication-selective adenovirus for the treatment of cancer: what have we learned?Gene Ther. 2001 Jan;8(2):89-98. doi: 10.1038/sj.gt.3301377. Gene Ther. 2001. PMID: 11313778 Review.
-
[Gene therapy and molecular therapeutic for head and neck cancer].Gan To Kagaku Ryoho. 2005 Dec;32(13):2046-51. Gan To Kagaku Ryoho. 2005. PMID: 16352927 Review. Japanese.
Cited by
-
Oncolytic Adenovirus for the Targeting of Paclitaxel-Resistant Breast Cancer Stem Cells.Viruses. 2024 Apr 5;16(4):567. doi: 10.3390/v16040567. Viruses. 2024. PMID: 38675909 Free PMC article.
-
Evolving Horizons: Adenovirus Vectors' Timeless Influence on Cancer, Gene Therapy and Vaccines.Viruses. 2023 Dec 3;15(12):2378. doi: 10.3390/v15122378. Viruses. 2023. PMID: 38140619 Free PMC article. Review.
-
Head and Neck Squamous Cell Carcinoma Vaccine: Current Landscape and Perspectives.Curr Issues Mol Biol. 2023 Nov 16;45(11):9215-9233. doi: 10.3390/cimb45110577. Curr Issues Mol Biol. 2023. PMID: 37998754 Free PMC article. Review.
-
Clinical Advances and Future Directions of Oncolytic Virotherapy for Head and Neck Cancer.Cancers (Basel). 2023 Nov 4;15(21):5291. doi: 10.3390/cancers15215291. Cancers (Basel). 2023. PMID: 37958464 Free PMC article. Review.
-
Modulation of Reoviral Cytolysis (I): Combination Therapeutics.Viruses. 2023 Jun 29;15(7):1472. doi: 10.3390/v15071472. Viruses. 2023. PMID: 37515160 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Other Literature Sources
Medical
Research Materials
Miscellaneous