Protection of mice by a λ-based therapeutic vaccine against cancer associated with human papillomavirus type 16

Abstract

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 × 1012 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. Conclusion: 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. Copyright © 2010 S. Karger AG, Basel