Cancer vaccine – OncovexGM-CSF
Numerous potential cancer vaccines have already been investigated, but with limited success
Numerous potential cancer vaccines have already been investigated, but with limited success. Another approach, oncolytic immunotherapy, has some potential, using herpes simplex-1. BioVex’s OncovexGM-CSF is an immune enhanced form of HSV-1, with genes that enable tumour selective replication and block antigen presentation having been deleted.1
The idea is that it will replicate selectively in tumours, which leads to the destruction of cancer cells, but will leave the healthy cells around them undamaged. It has also had the coding sequence for human granulocyte–macrophage colony stimulating factor inserted, with the aim of increasing the immune response to the tumour antigens that are released after the virus replicates, killing cancer cells throughout the body.
In a Phase II trial in 50 patients with stage IIIc and stage IV melanoma, most of whom had failed at least one previous therapy, subjects were given the virus as a stand-alone therapy.2 The overall response rate was 28%, with 10 patients experiencing a complete response, four a partial response, and a further 10 achieved stable disease for at least three months.
More than 90% of the responses were maintained for more than seven months – up to 31 months at the time of reporting. A further two patients achieved a complete response after surgery, and the overall survival rate was 58% at one year, and 52% at two years. Responses were seen in both injected and distant sites, including visceral organs.3
It is also being investigated as a possible treatment for head and neck cancer. In a Phase I/II study, a total of 17 subjects with advanced forms of the cancer were given the virus by direct injection into tumour-containing lymph nodes, at one of three dose levels, before surgery.4 It was well tolerated, and 93% of the subjects had a complete pathological response at surgery, with five achieving a rapid complete response after only two or three virus doses. After a median follow-up of 30 months, there was no local recurrence in the neck, and the survival rate at that point was 82%.
Phase III trials are already under way in melanoma, and are planned for patients with head and neck cancer.
references
1. B.L. Liu et al. Gene Ther. 2003, 10, 292
2. N.N.Senzer et al. J. Clin. Oncol. 2009, 27, 5763
3. H.L. Kaufman et al. Ann. Surg. Oncol. 2010, 17, 718
4. K. Harrington et al. J Clin Oncol, 2009, 27 (15, suppl), Abst. 6018
