ADVAXIS Lm TECHNOLOGY™

A Proprietary Antigen Delivery Platform that Activates the Immune System, Naturally

Advaxis’ investigational immunotherapies are designed to capitalize on the body’s ability to recognize and attack bacterial infections. Our core platform – Lm Technology™ – alters a live, attenuated strain of Listeria monocytogenes (Lm) bacteria to stimulate cancer-fighting T-cells directed against cancer antigens and reduce factors that protect the tumor microenvironment from immunologic attack and contribute to tumor growth.

Using the Body's Own Immune System to Fight Cancer

Advaxis’ proprietary Lm-based antigen delivery system uses live a highly attenuated, bioengineered strain of Listeria monocytogenes (Lm) bacteria to teach the immune system to view tumor cells as potentially bacterial-infected cells and eliminate them.

1

Lm-LLO Immunotherapy Infusion

After infusion into the patient, the Lm-LLO system accesses dendritic cells and other antigen presenting cells (APCs) directly inside each patient. The Lm-LLO enters the APC, following the natural immune system pathway.

2

LLO Mediated Escape

Once inside the APC, as part of its unique natural life cycle, the Lm escapes destruction and enters the cytoplasm. Here, via Advaxis’s bioengineering process, it produces tumor associated antigen (TAA), fused to highly immunogenic bacterial protein (tLLO), collectively, the “fusion protein.” This fusion protein is secreted by the Lm-based antigen delivery system directly into the cytoplasm of APCs.

3

Immune System Activation

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 along the MHC I pathway. The fusion protein is also responsible for neutralizing regulatory T-Cells and myeloid derived suppresser cells (MDSCs) which are protecting the tumor, to allow the CD8+ T-Cells to be effective against the tumor.

THE ADVAXIS DIFFERENCE

Lm Technology™ - Arming the immune system with the weapons it needs to fight cancer.

Starting with a live, attenuated strain of Listeria, through the Advaxis manufacturing process, multiple copies of a plasmid that encodes a fusion protein sequence including a fragment of the tLLO (listeriolysin O) molecule are joined to the cancer antigen of interest. The attenuated strain of listeria “infects” antigen presenting cells, and begins to secrete fusion protein.

This process has been shown to stimulate both the innate and adaptive arms of the immune system, while reducing tumor defense mechanisms, making it easier for the immune system to attack and destroy the cancer cells.

ADVAXIS™ INTELLECTUAL PROPERTY

We protect our proprietary Lm Technology™ with an extensive portfolio of issued and pending patents in the U.S. and worldwide. Since 2002, we have maintained, through various agreements, an exclusive worldwide license and a right to grant sub-licenses of our Lm Technology™ from the University of Pennsylvania.  In addition, we have 160 Advaxis-originated patents and growing, across multiple categories.

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