Viruses are small agents that only replicate inside living cells of the organism they infect. Some of them, called oncolytic viruses preferentially infect and kill cancer cells. Their use has been exploited in cancer therapy since early clinical trial studies in the 1940s-50s. However, for several years research in the field was delayed due to the lack of adequate technology. Recent advances in genetic engineering sped up research into the application of viruses for therapeutic uses. Canadian scientists have launched earlier this month the world's first clinical trial that uses a combination of two viruses to attack and kill cancer cells, and at the same time stimulate an anticancer immune response.
Canadian patients with incurable, advanced or metastatic solid tumors in which standard treatment have failed can now be enrolled in the world’s first clinical trial in which the safety and efficacy of a new combination therapy including two viral strains will be tested.
The two viruses being tested in this study are manufactured in specialized facilities at the Ottawa Hospital and McMaster University and have been called MG1MA3 and AdMA3. MG1MA3 is derived from the Maraba virus, isolated from Brazilian sandflies, while AdMA3 is a derivative of the Adenovirus, the common cold virus. Both viruses are engineered to specifically recognize and infect cancer cells that express on their surface the melanoma associated antigen 3 (MAGE-A3), a protein of unknown function that only tumor cells are able to produce.
This research has been transitioned to patients after both viruses showed the ability to selectively kill cancer cells in animals and to shrink human tumor samples by creating an immune response against the antigen contained in the viruses and expressed by infected tumor cells. In these experiments the viruses' tumor killing effect was potentiated when AdMA3 was given first to prime the immune system against the viral antigen.
The trial is expected to enroll about 79 patients across four Canadian hospitals. The Phase I/II study should take about three years during which the toxicity and safety first, then the efficacy of the viral therapy will be established. Initial responses are encouraging since the viral treatment seems to be better tolerated than chemotherapy and patients reported easily manageable symptoms resembling those of a standard flu. Patients will be split into three arms: some of them will receive either MG1MA3 or AdMA3 alone, whilst others will receive a combination of the two, since it is still not clear whether combination of the two viruses will improve the clinical outcome – measured as objective tumor response rate (ORR) – compared to treatment with each virus alone.
If successful, similar trials tailored to other types of tumors, including brain cancer and several devastating childhood cancers will be performed in the hope to find a more effective and better tolerated therapy.
Crown Bioscience is delighted to witness continuous progresses in immuno-oncology and will follow closely the MG1 Maraba/MAGE-A3 trial results.
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