APO010

 APO010’s potential value as a tool in immune therapy is strengthen by new data. A series of recent dramatic advances has demonstrated that the human immune system can kill cancer cells and can be an important player in the fight against cancer. The human immune system can kill cancer cells by use of a certain type of white blood cells called cytotoxic T lymphocytes CTLs. One of the way CTLs kill cancer cells in a process called programmed cell death (called apoptosis). By binding to a death receptor on the cancer cell a series of processes destructs the cancer cell. The CTLs bind to the cancer cell via a ligand called Fas ligand or Fas-L to a receptor (CD95) on the tumor cell. APO010 is synthesized as a mega FasL consisting of six FasL and the cancer cell sees this as if it was a cell, a CTL that binds to the cancer and the cancer cell can undergo apoptosis.

APO010_fig

 Illustration from: Cytotoxic T Cells, Mads Hald Andersen, David Schrama, Per thor Straten and Jürgen C. Becker Journal of Investigative Dermatology (2006) 126, 32–41.

 

The presence of the death receptor is however not enough to ensure cancer cell death. Whether the cancer cell is killed or not is more complex and this is where Oncology Ventures technology is important. By use of MPI’s drug response predictor DRP™ Oncology Venture can predict which patients will be most likely to respond to APO010 treatment.

APO010 has been in phase 1 and is now ready to enter a focused phase 2 in breast cancer, ovarian cancer or multiple myeloma.

Manufacturing APO010 is performed by use of the APO010 gene inserted into a CHO cell, the manufacturing is robust, a master cell bank in place. The company has APO010 clinical material vials in store but may need to commence a new manufacturing before starting a clinical trial.

APO010 is in-licensed to Oncology Venture from Onxeo (previously Topotarget).

APO010 was originally designed by professor Jurg Tschopp in Lausanne and developed by Apoxis SA.

Fas receptor agonist APO010 – from NCI (US) Drug directory

A recombinant, soluble, hexameric fusion protein consisting of three human Fas ligand (FasL) extracellular domains fused to the dimer-forming collagen domain of human adiponectin with potential pro-apoptotic and antineoplastic activities. Assembled into a soluble hexameric structure mimicking the ligand clustering of endogenous active FasL, Fas receptor agonist APO010 activates the Fas receptor, resulting in caspase-dependent apoptosis in susceptible tumor cell populations. FasL is a transmembrane protein of the tumor necrosis factor (TNF) superfamily and a pro-apoptotic ligand for the death receptor Fas.

 

License agreement for APO010

Oncology Venture has had the license to APO010 since 2012. Oncology Venture has all rights to APO010 transferred from TopoTarget (now Onxeo after the merger with BioAlliance Pharma).