Systemic delivery of current cytotoxic chemotherapy generally cannot differentiate between malignant and healthy cells, thus creating significant side effects and limiting its potential efficacy.
Due to the accelerated cell proliferation in the tumor, not all cells receive adequate blood supply, resulting in ischemia and increased apoptosis within the tumor.
theRecognizing this phenomenon, Aposense can utilize one of its apoptosis-targeting probes to carry a generic cytotoxic drug, with known activity, to achieve targeted delivery to the tumor, using already existing apoptotic cells within the tumor as the target.
The cytotoxic agent can then act on the surrounding tumor cells, while avoiding interaction with healthy tissues.
Another approach is to utilize ATT* high residence time in the plasma as an inactive depot to reduce toxicity and increase efficacy.
This approach is implemented for example in the ATT-11T anti-cancer compound (partnered with Teva Pharmaceuticals), where an ATT moiety is conjugated to the commercially available chemotherapeutic pro-drug irinotecan (which releases the topoisomerase I inhibitor SN-38). As shown below, both the efficacy and the plasma half-life of the active drug (SN-38) are significantly superior in the ATT-11T group compared to irinotecan.
* Aposense conjugates used for this approach are a modification of the ATT design.