Oestradiol enhances tumour regression induced by B7-1/IL-2 adenoviral gene transfer in a murine model of breast cancer.
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.
Dabrosin
C
C
Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada L8N 3Z5. lotda@imk.liu.se
Palmer
K
K
Gauldie
J
J
D000256:Adenoviridae; D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D007376:Interleukin-2 / Q000235:genetics* / Q000494:pharmacology*; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000473:pathology*; D051379:Mice; D010052:Ovariectomy / Q000662:veterinary; D014162:Transfection
D018122:B7-1 Antigen; D007376:Interleukin-2; D004958:Estradiol; D007371:Interferon-gamma