Lm-based Antigen Delivery System
Advaxis’ proprietary Lm-based Antigen Delivery System uses live, attenuated bioengineered Listeria monocytogenes (Lm) bacteria to stimulate the immune system to view tumor cells as potentially bacterial-infected cells and target them for elimination.
This system accesses dendritic cells and other antigen presenting cells (APCs) directly inside each patient to produce tumor associated antigen (TAA), fused to highly immunogenic bacterial protein, collectively, the “fusion protein.” This fusion protein is secreted by the Lm-based Antigen Delivery Platform directly into the cytoplasm of APC’s. Once secreted, the fusion protein triggers the patient’s own immune system to cross-present the TAA as a bacteria associated antigen, to generate a powerful cytotoxic (CD8+) t-cell response. The fusion protein is also responsible for neutralizing regulatory t-cells and myeloid derived suppresser cells (which are protecting the tumor) to allow the CD8+ t-cells to be effective against the tumor.
We start with a live, attenuated strain of Listeria, then add multiple copies of a plasmid that encodes a fusion protein sequence including a fragment of the LLO (listeriolysin O) molecule joined to the antigen of interest. This fusion protein is secreted by the Listeria inside antigen-presenting cells, which has been shown to result in a stimulation of both the innate and adaptive arms of the immune system that also reduces tumor defense mechanisms, making it easier for the immune system to attack and destroy the cancer cells.