The next step in tailored immunotherapy is the MINE™ (My Immunotherapy Neo-Epitopes) program, which is advancing under a clinical development and commercialization agreement between Amgen and Advaxis. MINE has the potential to provide patients with a truly customized approach to cancer treatment by stimulating an immune response against the unique mutations, or neoepitopes, contained in each individual patient’s tumor.

MINE™ technology leverages massive parallel sequencing and eliminates the need for predictive algorithms and enabling the development of truly tailored immunotherapies. 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 early 2017 using ADXS-NEO vectors to target patients’ unique, tumor-specific neoepitopes, in collaboration with Amgen.

Advaxis has joined the Parker Institute for Cancer Immunotherapy’s Tumor Neoantigen Selection Alliance (TESLA) consortium to further the development of effective neoantigen vaccines, such as the MINE™ platform, in targeting tumor epitopes that may function as optimal targets for cancer immunotherapies.