Therapeutic area

P17

Effect of P17 in cancer models:

The most significant antitumoral efficacy of P17 in vivo was that observed in mice bearing MC38 tumor treated with a single intratumoral injection of 108 vp Semliki Forest Virus vectors expressing IL-12 and 10 intraperitoneal doses of 75 mg of TGF-b inhibitor peptide p17. While SFV-enhIL-12 by itself was able to induce complete tumor regressions in 50% of tumors (n=32), the combination of SFV-enIL12 and p17 considerably increased this effect, inducing complete tumor regressions in 92% of tumors (n=26).

In a lung metastasis model it was determined P17 inhibits bone metastasis. In this model, intracardiac (ic) inoculation of lung cancer cells (M5) produces bone metastasis in nude mice. Analysis of the hind limbs of mice inoculated with highly metastatic M5 cell line revealed a decreased metastatic area in P17 treated animals compared with vehicle-treated mice.

Relevant publications:

Dotor J, Borras-Cuesta F, et al. “Identification of peptide inhibitors of transforming growth factor beta1 using a phage-displayed peptide library” Cytokine 39 (2007) 106–115.

Vicent S, Lecanda F, et al. “A Novel Lung Cancer Signature Mediates Metastatic Bone Colonization by a Dual Mechanism” Cancer Res 2008;68(7):2275–85.

Gil-Guerrero L, Lasarte JJ, et al. “In Vitro and In Vivo Down-Regulation of Regulatory T Cell Activity with a Peptide Inhibitor of TGF-b1” The Journal of Immunology, 2008, 181: 126–135.

Serrati S, Del Rosso M, et al. “TGFb1 antagonistic peptides inhibit TGFb1-dependent angiogenesis” Biochemical pharmacology 77(2009)813–825