In three distinct preclinical murine models of obesity (high-fat diet, aged-related ad libitum fed, and leptin-receptor deficient db/db mice), immunostimulatory therapy with anti-CD40 antibodies and IL-2 resulted in complete lethality in obese mice, while non-obese mice and calorie-restricted aged mice survived and showed a positive anti-tumour response (55, 60). This evidence concerns the gene IL2 and obesity due to melanocortin 4 receptor deficiency.