ADXS-NEO
The first immunotherapy candidate leveraging the MINE™ technology, ADXS-NEO, is a customized cancer treatment with promising implications across several cancers. Through a parallel manufacturing system, the production of ADXS-NEO is designed to be easily scalable, cost-effective, and timely for patients. Further details on the potential of ADXS-NEO can be found in new white paper.
Developing the ADXS-NEO immunotherapy begins with a biopsy of the primary tumor and/or metastases, along with the patient’s normal cells, to identify non-synonymous mutations, or neoepitopes. These are then sent for exome sequencing, where a mutational map of the tumor is developed that can be used to select a set of neoepitopes most likely to be immunogenic.
Advaxis uses its Lm Technology™ to integrate coding sequences for these tumor-associated neoepitopes into a plasmid-based system that expresses them in the context of a fusion protein sequence including a fragment of the LLO molecule. The Lm vector is taken up by the antigen-presenting cells. Within the vector, large quantities of proteins with the mutated neoepitope are generated and secreted into the cytosol of the antigen-presenting cells, wherein they are processed and used to activate tumor-specific T cells, which can then find the cancer cells and destroy them. ADXS-NEO constructs also are designed to neutralize tumor protecting mechanisms by reducing the immune-suppressive activities of Tregs and myeloid-derived suppressor cells in the tumor microenvironment. Because the immune response is activated only against the mutated neoepitopes, little-to-no systemic blockade of tolerance and no off-target toxicity is expected.
The MINE program is expected to enter the clinic in 2017 using ADXS-NEO vectors to target patients’ unique, tumor-specific neoepitopes, in collaboration with Amgen.
