Listeria-based Immunotherapy

Listeria monocytogenes (Lm) is a species of bacteria with attributes that give it great potential as an immunotherapy vector.

In the body, Listeria are taken up by the immune system’s antigen-presenting cells (APCs), where they have a unique ability to escape the APC’s normal defenses and replicate.

Scientists are harnessing these attributes by engineering a weakened strain of Listeria that functions as an immunotherapy vaccine. The bacteria used in the vaccine are designed to expresses tumor-associated antigens, which are processed by the APC’s’ immune machinery and presented to T cells. This primes the T cells to recognize and attack other cells that present the same antigens. The vaccine can also be personalized to express specific tumor-associated antigens found in individual patients. Listeria-based immunotherapy is still an investigational modality, but encouraging results have been observed in early-stage clinical studies.

Amgen is collaborating with Advaxis to develop ADXS-NEO, an immunotherapy platform that combines Advaxis’ Lm-based antigen delivery system with a second novel technology called MINE™ (My Immunotherapy Neo-Epitopes). The Listeria used in ADXS-NEO are engineered to include DNA plasmids that produce the same tumor neo-antigens – mutated protein fragments – found in a patient’s tumor cells but not in healthy cells. Once injected into the patient, the Listeria are taken up by antigen-presenting cells, or APCs (1), where the bacteria secrete tumor-associated antigens into the liquid interior of the APC (2). The antigens are then processed and presented to T cells (3). The goal is to help T cells recognize a wide range of tumor-associated antigens and attack cancer cells with the same antigens (4).

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