Mode of Action

Tigilanol tiglate is a potent cellular signalling molecule with a multifactorial mode of action

Following injection into the target tumour, tigilanol tiglate activates a complex series of cellular signalling cascades that result in:

  • destruction of the treated tumour mass; and,
  • stimulation of healing responses in tissues surrounding the treatment site.

These signalling cascades, some of which are dependent on activation of specific classical isoforms of protein kinase C (PKC), operate by inducing:

  • a rapid, acute and highly localised inflammatory response in and immediately surrounding the tumour mass;
  • recruitment of immune cells to the treatment site;
  • disruption of the integrity of the tumour vasculature;
  • immunogenic tumour cell death resulting in the release of danger associated molecular patterns (DAMPs) and tumour antigens; and,
  • upregulation of gene and protein expression associated with enhanced wound healing in normal tissue surrounding the treatment site.

There is also preliminary evidence from in vitro studies and from clinical observation of potential anenestic responses (i.e. shrinkage or destruction of non-injected tumours) in a number of human and canine patients, suggesting induction of an antigen-specific immune response associated with some immunogenic tumour types. 

Tigilanol tiglate is 'tumour agnostic'

Because this mode of action relies in significant part on treatment response by the ‘host’ cells (e.g. immune cell recruitment, effects on tumour vasculature), rather than intrinsic sensitivity of the cancer cells per se, tigilanol tiglate can be considered 'tumour agnostic' and has potential for efficacy against a range of different tumour types, irrespective of cells of origin or specific cancer gene mutations.

An overview of our current understanding of the mode of action of tigilanol tiglate from both in vivo and in vitro studies is illustrated below.

Tigilanol tiglate - Mode of Action