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Oestradiol enhances tumour regression induced by B7-1/IL-2 adenoviral gene transfer in a murine model of breast cancer.

Authors
  • Dabrosin, C
  • Palmer, K
  • Gauldie, J
Type
Published Article
Journal
British journal of cancer
Publication Date
Jul 21, 2003
Volume
89
Issue
2
Pages
385–390
Identifiers
PMID: 12865933
Source
Medline
License
Unknown

Abstract

The majority of breast cancers are oestrogen dependent and although current treatment strategies have improved, approximately 50% of the patients will develop metastasis. New treatments that result in long-term systemic immunity are therefore being developed. We have previously shown that adenoviral gene transfer of B7-1/IL-2 to murine breast cancer induces a high rate of complete tumour regression and systemic immunity. Since oestrogens not only affect breast cancer but also have been shown to modulate immune function and secretion of immune-regulatory cytokines, we explored whether administration of oestradiol altered the immune response induced by an adenoviral vector expressing B7-1/IL-2. An oestrogen-dependent murine breast cancer tumour was used in ovariectomised mice, supplemented either oestradiol or placebo. We report the somewhat unexpected finding that intratumoral injection of adenovirus expressing B7-1/IL-2 induces complete tumour regression in 76% of oestradiol-supplemented mice, while only 18% of the tumours regressed in the oestrogen-depleted group. Cured mice in both groups exhibited a similar CTL response against the tumour antigen. However, intratumoral IFN-gamma levels, 2 days after B7-1/IL-2 injection, were significantly higher in mice treated with oestradiol compared to placebo. This may be one mechanism explaining the higher response rate of tumours in oestradiol-replenished mice.

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