The pioneering science behind AVB-620 was developed in the lab of Nobel Laureate Roger T. Tsien at the University of California – San Diego. The initial motivation behind the invention was to enable systemic delivery of cell-penetrating peptides (CPP) and attached cargo to cancer cells. Avelas has utilized this approach by designing AVB-620 to deliver a fluorescent marker specifically to cancer cells for real-time cancer detection during surgery.
The approach involves activatable CPPs (ACPPs) which exploit cancer’s inherent biochemical pathology using enzyme activation to selectively deliver imaging cargo to target tissue. Protease enzymes associated with cancers activate the ACPP molecules, allowing the cargo to be delivered locally to malignant cells.
In the case of AVB-620, the novel peptide is cut by a subset of matrix metalloproteinases (MMPs) on cancer cells’ surface. This cleavage activity results in the unmasking of the molecule’s CPP and is also accompanied by a fluorescent color change. The CPP enters the surrounding cancer cells where it emits at this new wavelength. Avelas’ differentiated method of imaging measures the ratio of “active” CPP in cancer cells to that of “inactive” AVB-620 in surrounding tissue to provide surgeons an accurate image of cancer margins.
Avelas’ ACPP technology has several distinctive advantages:
- Using enzyme activity as the targeting mechanism provides molecular and biological amplification and results in high sensitivity
- The activatable agent masks the CPP until near target tissue, which enhances bio-distribution
- The cargo containing CPP triggers cellular binding and internalization resulting in enhanced cargo retention and extended imaging window
- The platform is general and modular allowing for broad applications