Defence Therapeutics Inc. announced the publication of a peer-reviewed study on the anticancer properties of its unconjugated AccuTOX, one of Defence's lead products engineered to treat established solid tumors. The study, which was published in the prestigious Journal of Translational Medicine, is entitled, "Local delivery of AccuTOX synergises with immune-checkpoint inhibitors at disrupting tumor growth". The Accum®?

platform was initially designed to accumulate biomedicines in target cells by inducing endosomal-to-cytosol escape. Interestingly however, the use of unconjugated Accum®? was observed to trigger cell death in a variety of cancer cell lines; a property further exploited in the development of Accum®?-based anti-cancer therapies.

Despite the impressive pro-killing abilities of the parent molecule, some cancer cell lines exhibited resistance. This prompted to test additional Accum®? variants, which led to the identification of the AccuTOX®?

molecule. From that perspective, AccuTOX®? holds many advantages over the parent Accum®?

entity: it exhibits enhanced killing potency while retaining the innate function of endosomal- to-cytosol escape, the molecule can be easily manufactured, it can be linked to antibodies as an in situ cleavable anticancer molecule (to increase its specificity), and iv) it is highly versatile, as it targets multiple intracellular pathways that are highly relevant to cancer growth and progression. The key highlights of the AccuTOX® study are: AccuTOX® is therapeutically superior to parent Accum® (both in vitro and in vivo); The molecule induces cell death of various murine and human cancer cell lines (T-cell lymphoma, colon, melanoma, lung and breast); AccuTOX® triggers the intracellular production of reactive oxygen species and disrupts endosomal membranes; Following contact with AccuTOX®, cancer cells die through a process called immunogenic cell death; The compound leads to similar responses in both male and female animals with no apparent toxicity; AccuTOX® enhances antigen presentation (tumor becomes visible to immune cells) Intratumoral administration of AccuTOX® to lymphoma, melanoma or breast cancer synergises with common immune-checkpoint inhibitors leading to efficient tumor growth control. In summary, unconjugated AccuTOX® could be used as an anti-cancer molecule.

The triggered effects are interesting and unexpected as the induction of immunogenic cell death brings an additional immune component to the equation, which may turn a "cold" into a "hot" tumor with increased infiltration of immune cells as shown in the published study. With FDA clearance to initiate a Phase I trial, Defence recently submitted a CTA application to Health Canada to widen the scope of clinical testing.