TRIPOKIN (IL2-L19-TNF)

TRIPOKIN (IL2-L19-TNF)

Tripokin (IL2-L19-TNF) is a fully-human immunostimulatory product consisting of the human vascular targeting antibody L19 that recognizes the alternatively spliced EDB domain of fibronectin, simultaneously fused to both human interleukin 2 (IL2) and human tumor necrosis factor alpha (TNFa). IL2 is a cytokine that stimulates immune effector cells, while TNF is a strong pro-inflammatory cytokine.
Considering that TNF is ten times more potent than IL2, to match the biological activity of the two cytokines a single point mutation in the TNF moiety was introduced.
The rationale for the development of this product relies on the fact that the combination of IL2- and TNF- based immunocytokines showed a strong synergistic effect in both pre-clinical and clinical studies.

SELECTED REFERENCES

De Luca et al. (2017) Mol Cancer Ther, 16(11); 2442–51;
Danielli et al. (2015) Cancer Immunol. Immunother. 64, 999-1009;
Hemmerle and Neri (2013) Br. J. Cancer 109 (5) 1206-13;
Schwager et al. (2013) J. Invest. Dermatol., 133, 751-8;
Papadia et al. (2013) J Surg Oncol., 107, 173-179;
Eigentler et al. (2011) Clin. Cancer Res., 17, 7732-42;
Balza et al. (2006) Clin. Cancer Res., 12, 2575-2582;
Borsi et al. (2003) Blood, 102, 4384-4392.

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