In Vivo Antitumor Activity of a Recombinant IL7/IL15 Hybrid Cytokine in Mice

作者：Song, Yinhong; Liu, Yalan; Hu, Rong; Su, Min; Rood, Debra; Lai, Laijun^*

来源：Molecular Cancer Therapeutics, 2016, 15(10): 2413-2421.

DOI：10.1158/1535-7163.MCT-16-0111

• T-CELL EXPANSION
• ADOPTIVE IMMUNOTHERAPY
• HUMAN INTERLEUKIN-7
• GROWTH-FACTOR
• GM-CSF
• IL-15
• CANCER
• BLOCKADE
• PROLIFERATION
• LYMPHOPOIESIS

Both IL7 and IL15 have become important candidate immunomodulators for cancer treatment. However, IL7 or IL15 used alone suffers from shortcomings, such as short serum half-life and limited antitumor effect. We have cloned and expressed a recombinant (r) IL7/IL15 fusion protein in which IL7 and IL15 are linked by a flexible linker. We then compared the antitumor effect of rIL7/IL15 with the individual factors rIL7 and/or rIL15. We show here that rIL7/IL15 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, rIL7/IL15-treated DCs had higher expression of costimulatory molecules CD80 and CD86. The higher antitumor activity of rIL7/IL15 is likely due to its longer in vivo half-life and different effects on immune cells. Our results suggest that rIL7/IL15 may offer a new tool to enhance antitumor immunity and treat cancer.

• 出版日期2016-10-1
• 单位三峡大学