Epitope spreading can get triggered by live, attenuated Listeria vaccine

Oct 8 2009

Advaxis, Inc. (OTCBB: ADXS), the live, attenuated Listeria monocytogenes (Lm) vaccine company, in collaboration with its scientific founder and Scientific Advisory Board Chair Dr. Yvonne Paterson, have shown that epitope spreading occurs in response to a form of the Company’s proprietary technology that targets tumor blood vessels (anti angiogenic antigen). Epitope spreading occurs when the immune system is able to attack antigens that are not the original target of an immune therapy but released from tumor cells killed by the therapy. By creating new targets in this way, the immune system can attack more antigens than the one for which the therapy was initially designed; thus, expanding the immune response against a tumor.

This addresses a problem that may occur when tumors mutate away from an immune attack. Escape mutations can develop over time and prevent an immunotherapy from working. Epitope spreading is a mechanism which can provide a continued therapeutic response when escape mutations arise in one or another antigen.

In research published earlier this year (Seavey et al 2009. J. Immunol. 182: 5537–46), and updated last week (Seavey & Paterson, 2009. BCTT. 1:19-30), a live Lm vaccine using the anti-angiogenic target VEGFR2 (Flk-1) fused to the Listeria protein listeriolysin O (LLO) was administered to mice. This vaccine not only attacked its target antigen but induced immune activation against a different tumor antigen Her2/neu, even though the vaccine did not target Her2/neu. Further, this vaccine attacked both tumor blood vessel formation and directly attacked tumor cells that displayed Her2.

“We know that Lm-LLO vaccines do many useful therapeutic things simultaneously; including strong immune activation, therapeutically altering the tumor microenvironment to make it more responsive to immune attack, inducing the synthesis of new immune cells, to name a few,” said Dr. John Rothman, EVP of Science & Operations at Advaxis. “The finding of epitope spreading adds to the growing list of therapeutic mechanisms associated with live Lm therapy.”

http://www.advaxis.com/