Protection of mice by a λ-based therapeutic vaccine against cancer associated with human papillomavirus type 16.
OBJECTIVE
Human papillomavirus (HPV) oncoproteins (i.e. E6 and E7) are constitutively expressed in cervical cancer cells. The proteins are ideal targets to be used for developing therapeutic vaccines against existing HPV-associated carcinomas. To date, whole bacteriophage ('phage')-λ particles, rather than purified 'naked' DNA, have been described as highly efficient delivery vehicles for a DNA vaccine.


METHODS
In this study, a safe and efficient λ-based therapeutic cancer vaccine, recombinant λ-ZAP E7 phage, was developed by inserting a HPV16 E7 gene into the Lambda ZAP® cytomegalovirus vector. λ-ZAP E7 phages were employed to immunize mice against the E7-expressing murine tumor cell line (TC-1), which is used as a tumor model in an H-2b murine system.


RESULTS
The tumor-bearing mice indicated a significant inhibition of tumor growth after 3 injections of 2 × 10(12) particles of recombinant phages. Released lactate dehydrogenase, interferon-γ and granzyme B from spleen cells and lymphocyte proliferation of spleen cells, which all demonstrate the enhancement of cell-mediated immunity, suggested the phages could be a potent gene delivery system in animal models.


CONCLUSIONS
Our results suggest the recombinant phages can be used as effective biological tools for inducing E7-specific protective immune responses. Hence, the study introduces a possible therapeutic strategy against cervical cancer and other HPV-related neoplasia.
Faculty of Medicine, Golestan University of Medical Sciences and Health Care, Gorgan, Iran.
Amir
A
Ghaemi
Hoorieh
H
Soleimanjahi
Pooria
P
Gill
Zuhair M
ZM
Hassan
Soodeh
S
Razeghi
Maryam
M
Fazeli
Seyed Mohammad H
SM
Razavinikoo
D000818:Animals; D010582:Bacteriophage lambda / Q000235:genetics*; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000276:immunology*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D016896:Treatment Outcome
D019496:Cancer Vaccines; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; C059731:oncogene protein E7, Human papillomavirus type 16