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Cancer Neoantigen Genetic Vaccines
Explore our cancer neoantigen genetic vaccine platform
We combine the use of viral vectors that have been engineered and optimized to express artificial genes encoding high-dimensional strings of human neoantigens, with state-of-the art bioinformatics for cancer neoantigen prediction. The unprecedented neoantigen-encoding capacity of our platform and its ability to efficiently and consistently express large numbers of neoantigens, provides significant advantages over other strategies, offering a unique approach to the potentiation of human anti-tumor immune responses.
An off-the-shelf neoantigen genetic vaccine for dMMR/MSI tumors
Tumors associated with Mismatch Repair Deficiency (dMMR) and Microsatellite instability (MSI) accumulate insertion/deletion mutations (indels) that are predictable as they principally arise at mononucleotide repeats. These indel mutations in coding regions result in a translational shift that generate frame shift peptides (FSPs). FSPs are highly immunogenic and may be safely utilized in vaccines as they bear no resemblance to natural protein sequences found in the human proteome. As such, they are ideal tumor-specific neoantigens.
As these mutations are targeted to a limited number of genes across the genome, several of them are shared across different patients. MSI-associated tumors consequently offer a unique opportunity for an ‘off-the-shelf’ vaccine.
NOUS-209 encodes 209 unique FSP cancer neoantigens found in different MSI tumor types. It has the potential to be the first ‘off-the-shelf’ cancer genetic vaccine to be tested in humans.
The enrollment in the first-in-human NOUS-209 Phase I clinical study commenced in Q4 2019.
Personalized cancer neoantigen genetic vaccine
NOUS-PEV is a personalised cancer genetic vaccine based on patient-specific neoantigens sourced from individual patient tumor mutanomes. The technology may be applied to any cancer indication where a tumor biopsy is available that is suitable for next-generation sequencing (NGS). The Company’s initial studies will in the first instance target tumors with high frequencies of somatic mutations, such as advanced non-small cell lung cancer (NSCLC), melanoma, and urothelial cancers (UC).
Nouscom has developed a robust and rapid 6 week needle-to-needle vaccine manufacturing process from the time of patient biopsy to vaccine production. This process allows for the assembly of strings of over 60 unique patient mutanome-specific neoantigens within a single genetic vaccine vector and the production of small patient-specific quantities of personalized vaccine.
NOUS-PEV is expected to enter clinical studies in 2020.
Next-generation targeted and armored herpes oncolytic virus
We combine the specificity of monoclonal antibodies with the cell-killing ability of wild type Herpes Virus to create next-generation cancer-specific oncolytic viruses with improved efficacy and safety. The ability of NOUS-THV-001 to express immunomodulatory molecules within tumor site further potentiates anti-cancer immune responses.
Novel, fully replicative, oncolytic Herpes Virus with a specific tropism for cancer cells
NOUS-THV-001 is an oncolytic virus that is able to kill cancer cells by invoking immunogenic cell death.
The proprietary virus developed by Nouscom has been de-targeted from its natural receptors and re-directed to attack tumor cells, resulting in the recruitment of T cells locally at the tumor site and the activation of T cells within the immediate tumor microenvironment, resulting in the death of uninfected cancer cells at distant sites.
NOUS-THV-001 can be potentiated by encoding transgenes that encode a range of different immunomodulatory molecules to enhance and broaden it’s anti-tumor effect.
NOUS-THV-001 has been engineered to bind tumor cell-surface antigen receptors, to accumulate at the site of the tumor, and to selectively infect and kill cancer cells. Virus-induced cell lysis results in the release of tumor neoantigens that are captured and presented by antigen presenting cells (APCs) that stimulate the proliferation of cancer-specific T cells. These may in turn attack and kill additional cancer cells, including uninfected ones at distal sites, thereby amplifying the initial anti-tumor effect of NOUS-THV-001.