In vivo antitumor Activity of a Recombinant IL-7/IL-15

Both IL-7 and IL-15 have become important candidate immunomodulators for cancer treatment. However, IL-7 or IL-15 used alone suffers from shortcomings, such as short serum half-life and limited antitumor effect. We have cloned and expressed a recombinant (r) IL-7/IL-15 fusion protein in which IL-7 and IL-15 are linked by a flexible linker. We then compared the antitumor effect of rIL-7/IL-15 with the individual factors rIL-7 and/or rIL-15. We show here that rIL-7/IL-15 has a higher antitumor activity than the combination of the individual factors in both murine B16F10 melanoma and CT-26 colon cancer models. This was associated with a significant increase in tumor infiltration of T cells, DCs and NK cells and a decrease in regulatory T cells (Tregs). In addition, rIL-7/IL-15-treated DCs had higher expression of costimulatory molecules CD80 and CD86. The higher antitumor activity of rIL-7/IL-15 is likely due to its longer in vivo half-life and different effects on immune cells. Our results suggest that rIL-7/IL-15 may offer a new tool to enhance antitumor immunity and treat cancer.

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