DODEKIN

DODEKIN

Dodekin is a fully-human immunostimulatory product consisting of a vascular targeting antibody fused to the human cytokine interleukin-12 (IL12).

Recombinant IL12 has potent anti-cancer activity, but its therapeutic use is limited by associated toxicities. However, the site-selective delivery of IL12 to the sub-endothelial extracellular matrix in tumor blood vessels allows to drastically improve the therapeutic index of this cytokine.

Quantitative biodistribution studies of Dodekin have shown a preferential uptake of the molecule in tumor tissues compared to healthy organs. Preclinical studies in several immunocompetent murine models of cancer have shown that this immunocytokine has a potent anti-tumor activity and is able to induce long-lasting tumor eradication. It further potentiates the action of other therapeutic agents such as immunological checkpoint inhibitors.

In a recently established collaboration with the University Hospital Zurich, the murine surrogate of Dodekin has demonstrated a striking single-agent anti-cancer activity in preclinical models bearing orthotopic glioblastoma. The treatment induced long-term tumor eradications in a substantial proportion of the treated animals.
 
ONGOING CLINICAL TRIALS

  • A phase I study to evaluate safety and early signs of efficacy of Dodekin in patients with advanced solid carcinomas and DLBCL after previous immune-checkpoint blockade therapy (NCT04471987).

SELECTED REFERENCES

Weiss et al., (2020) Sci Transl Med, 12 (564):eabb2311
Puca et al. (2020) Int J Cancer, 146, 2518-30
Hutmacher et al. (2019) Cancer Immune Res, 7, 572-83
Ongaro et al. (2019) J Biotechnol, 291, 17-25
Mosely et al. (2017) Cancer Immunol Res, 5, 29-41
Hemmerle & Neri (2014) Int J Cancer, 134, 467-77
Lasek et al. (2014) Cancer Immunol Immunother, 63, 419-35
Pasche et al. (2012) Clin Cancer Res, 12, 4092-103
Sommavilla et al. (2010) Protein Engin Des Sel, 23, 653-61
Gafner et al. (2006) Int J Cancer, 119, 2205-12
Halin et al. (2003) Cancer Res, 63, 3202-10
Halin et al. (2002) Nat Biotechnol, 20, 264-9
Castellani et al. (2002) Am . Pathol, 161, 1695-1700

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