Poster Presentation 6th Australian Health and Medical Research Congress 2012

Efficacy and mechanism of action of a novel anti-cancer agent EBC-46 on human and mouse tumors. (#332)

Marjorie M. A. de Souza 1 , Glen M. Boyle 1 , Carly J. Pierce 1 , Paul W. Reddell 2 , Peter G. Parsons 1
  1. Queensland Institute of Medical Research, Herston, QLD, Australia
  2. QBiotics Limited, Yungaburra, Queensland, Australia

Surgery and radiation are the mainstays of local treatment of tumors but are limited with respect to efficacy and safety. There is a need for new and improved forms of therapy. Previous work in this laboratory has shown that topical application of a protein kinase C activator (diterpene ester) has cured subcutaneous tumours in mice, with a favourable cosmetic outcome. It primarily involves a neutrophil – dependent host inflammatory response; a biological characteristic of diterpene esters.

EBC-46 is a novel diterpene ester that activates protein kinase C (PKC). It induces the translocation of PKC to the plasma membrane where it interacts with substrates involved in signal transduction pathways that regulate cellular activities such as growth, differentiation, migration, proliferation and inflammatory responses. EBC-46 shows a unique profile of specificity for the different isoforms of PKC present in the cytoplasm. A single intratumoral injection of EBC-46 locally ablates tumors in mice, either human xenografts or syngeneic mouse tumors, accompanied by a strong host immune response which includes an influx of neutrophils. Ex vivo cultures of the respective tumors and immunohistochemical analysis of the same, have shown rapid disintegration of tumor cells by 4 – 8 hours after treatment, resulting in complete loss of viable cells between 5 – 7 days.

This drug is distinguished from others by triggering a rapid and destructive host response at and around the tumour site with no discernable adverse effects. It has potential as a palliative treatment aiming for local disease control or adjuvant therapy preceding surgery or radiation.