Development and initial clinical studies of TA-HPV in cervical cancer

Borysiewicz, L. K., Man, Stephen Tzekwung ORCID: https://orcid.org/0000-0001-9103-1686, Nimako, M., Wilkinson, Gavin William Grahame ORCID: https://orcid.org/0000-0002-5623-0126, Fiander, Alison Nina, Lehner, P., Wang, C. Y., Westmoreland, D., Stacey, S., Hickling, J. and Ingles, S. 1995. Development and initial clinical studies of TA-HPV in cervical cancer. European Journal of Cancer 31 (supp 3) , p. 17. 10.1016/0959-8049(95)99882-z

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Abstract

Cervical cancer is associated with human papillomavirus (HPV) infection in >94% of cases, usually HPV strain 16 or 18. In the transformed cells continued expression of two intra-cellular, non-structural viral proteins, termed E6 and E7, is required to maintain the malignant phenotype. These proteins are potential targets for immunotherapy, particularly by cytotoxic T cells.A recombinant (TA-HPV) was made, in which E6 and E7 genes of both strains were fused and inserted into Wyeth strain vaccinia. Furthermore E7 was modified to inactivate the Rb binding site, largely removing its oncogenic potentialThis construct has been used to vaccinate 8 patients with established cervical cancer, under contained environmental release conditions. Clinical follow up is still in progress but no side effects of vaccination have been observed, after up to a year, despite subsequent chemo- and radio-therapy. No environmental contamination has been detected and the recombinant is stable after human inoculation.Serological response to the inserted sequences has been observed in 3 of 3 patients. Assays for human HPV specific CTL are difficult but we have developed an assay, using adenovirus recombinants expressing HPV E6 & E7 for in vitro expansion of CTL from PBMC. Studies are in progress to determine if TA-HPV induces this specific response in vaccine recipients.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > R Medicine (General) R Medicine > RZ Other systems of medicine
Publisher:	Elsevier
ISSN:	0014-2964
Last Modified:	14 Nov 2022 08:15
URI:	https://orca.cardiff.ac.uk/id/eprint/67713

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