Advaxis's Listeria-based Lm-LLO Immunotherapy Featured in Nature Biotechnology December 11, 2014 PRINCETON, N.J., Dec. 11, 2014 (GLOBE NEWSWIRE) -- Advaxis, Inc. (Nasdaq:ADXS), a clinical-stage biotechnology company developing cancer immunotherapies, announced today that its Lm-LLO immunotherapy technology is featured in an article in the December 2014 issue of Nature Biotechnology. Entitled "Listeria vaccines join the checkpoint frenzy," the article explores the potential of the Listeria bacterium as a vector to enhance an anti-tumor response given its ability to induce powerful innate and adaptive immune responses. Nature Biotechnology is the leading peer-reviewed scientific journal in the field of biotechnology. The monthly journal publishes peer-reviewed research results, as well as expository articles on the commercial business sector of the biotechnology field. Advaxis is featured in the article as one of the leading companies pursuing Listeria-based cancer immunotherapies. Advaxis's Lm-LLO immunotherapy technology is recognized as being unique in the field of immunotherapy drug development in that it uses a live, attenuated bacterial platform genetically engineered to attack cancer tumors and minimize toxicity. In the article, Laurence Wood, Ph.D., assistant professor in the Department of Immunotherapeutics and Biotechnology at the Texas Tech University Health Sciences Center in Abilene, stated that, "Interest from big pharma is a huge deal. Down the road, there will likely be even greater interest in getting bacterial-based cancer vaccines through clinical trials, alone or in combination with other drugs." "One major advantage of Listeria is that it readily gets into and thrives in the cytosol of antigen-presenting cells," adds Dr. Wood in the article. "It is early days, but the revived interest could be warranted. That Listeria based vaccines have shown improved or similar efficacy to standard of care with far fewer adverse events is incredibly promising." Further, the article highlights the observation that Advaxis's Lm-LLO platform is designed in a manner that potentially produces an immune response at a lower dose and makes it easier to combine with other immunotherapy technologies, such as checkpoint inhibitors. David J. Mauro, M.D., Ph.D., Executive Vice President and Chief Medical Officer of Advaxis, commented, "The potential of Listeria-based cancer immunotherapies is gaining increasing interest within the oncology field as a promising route to developing a host therapies, and, as evidenced by this article in Nature Biotechnology, Advaxis's Lm-LLO platform and rapidly advancing pipeline of compounds are viewed as clear leaders within the industry. Additionally, as the article notes, the advantages that our Lm-LLO technology offers as a combination therapy makes it attractive to potential development partners with checkpoint inhibitor technologies. This attribute was key to the two development agreements that we initiated with MedImmune and Merck, both of which we look forward to advancing to the clinic in early 2015."
Treatment with Lm-LLO immunotherapies lead to decreased Tregs and MDSC in the tumor microenvironment. The Journal of Immunology, 2012, 188, 165.12 Bioengineered Listeria monocytogenes (Lm), which secrete antigens fused to a fragment of listeriolysin O (LLO) have been shown to be effective cancer immunotherapeutics in several mouse models of cancer, and are currently being evaluated in Phase 2 clinical trials for HPV-associated dysplasia and malignancies. Treatment with Lm-LLO immunotherapies results in a marked increase in tumor infiltrating lymphocytes, in particular CD8+T cells. The antigen-specific CD8+T cells have been observed to kill tumor cells in vitro, showing the functionality of the Lm-stimulated T cells. Lm-LLO immunotherapies also have an impact on suppressor cells in the tumor microenvironment. In various tumor models, treatment results in a decrease in the ratio of regulatory T cells (Tregs) to effector T cells in the tumors. Here, we report a corresponding decrease in the ratio, and number, of monocyte-derived suppressor cells (MDSCs) after Lm-LLO immunotherapy. These change are only seen in the tumor microenvironment. Further, both Tregs and MDSCs isolated from the tumor have a decreased ability to suppress the division of T cells after Lm-LLO immunotherapy. However, there is no change in functional ability of splenic Tregs or MDSCs. Thus, the efficacy of Lm-based immunotherapies on tumors is likely due to a combined increase in antigen-specific effector cells and a tumor specific decrease in the numbers and function of suppressor cells in the tumor microenvironment.
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