An international research group led by the University of Basel has developed a promising strategy for therapeutic cancer vaccines. Using two different viruses as vehicles, they donated specific tumor components in experiments on cancerous mice to stimulate their immune system to attack the eardrum. The approach is now being tested in clinical trials.
Using the immune system as an ally in the fight against cancer is the basis of a wide range of modern cancer therapies. One of these is the therapeutic cancer vaccine: after diagnosis, experts began to determine which parts of the eardrum may act as a signaling factor for the immune system. The patient is then administered directly these components through vaccination, with a view to stimulating the strongest immune response against the tumor.
Viruses transmitted harmlessly are used as vehicles to transport the normal tumor molecules into the body. In the past, however, many attempts to create this type of cancer treatment have failed due to an adequate immune response. One of the obstacles is that the tumor is made up of the body’s own cells, and the immune system takes safety measures so that you don’t attack those cells.
In addition, the immune cells often attack the “foreign” virus vehicle more aggressively than the body’s own carriers. With almost all cancers of this type developed to date, therefore, the desired effect on the eardrum has not been successful. Finding the right vehicle is just as relevant in terms of effectiveness as the choice of tumor part as the point of attack.
Arenaviruses as vehicles
The research group led by Professor Daniel Pinschewer of the University of Basel had already found in previous studies that viruses from the arenavirus family are highly suitable as vehicles for stimulating a strong immune response. The group now reports in the magazine Cell reports treatment that the combination of two different arenavirus yielded promising results in animal experiments.
The researchers focused on two viruses at a distance called Pichinde virus and lymphocytic choriomeningitis virus, which they modified through molecular biological methods for use as vaccine vectors. When they took the method of administering the selected tumor part first with the same virus and then, at a later time, with the other, the immune system moved the attacker away from the vehicle and more towards the cargo.
By using two different viruses, one after the other, we target the stimulated immune response to the true target, the tumor molecule. “
Daniel Pinschewer, Professor, University of Basel
Removed or reduced tumor
In experiments with mice, the researchers were able to measure the strong activity of killer T cells that destroyed the cancer cells. In 20% to 40% of the animals – depending on the type of cancer – the tumor disappeared, while in other cases the tumor growth rate was at least temporary.
“We can’t say anything about the effectiveness of our approach in humans so far,” Pinschewer says. However, ongoing studies with cancer treatment based on a single arenavirus have already shown promising results. that the effect on tumors in animal experiments directly translates the effect on corresponding types of cancer in humans. ”However, because the treatment with two different viruses works better in mice than the cure with just one virus, the results of our research leave me optimistic, “Pinschewer adds.
The biotechnology company Hookipa Pharma, of which Pinschewer is one of the founders, is now studying the effectiveness of this new approach to cancer treatment in humans. “We are currently exploring what our stand-alone approach can achieve,” says the researcher. “If successful, a wide range of combinations with conventional therapies were expected, including the individual devices come together to eliminate tumors even better. “
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Magazine Reference:
Bonilla, WV, et al. (2021) A major heterologous arenavirus vector stimulus overcomes autoimmunity for specific effective tumor CD8 T cell invasion. Cell reports treatment. doi.org/10.1016/j.xcrm.2021.100209.