Dr. Nadine van Montfoort – Dr. Christianne Groeneveldt | The Future of Cancer Treatment with Reovirus and Immunotherapy

It is suggested that most people have been exposed to Reo at some point in their lives, leading to the presence of neutralizing antibodies which could interfere with the therapeutic action of the virus.

Dr. Nadine van Montfoort and colleagues at Leiden University Medical Center have made significant strides in understanding the potential of Reo in cancer treatment. In a recent study, coordinated by Dr. Christianne Groeneveldt, van Montfoort’s team confirmed that over 80% of both healthy individuals and cancer patients have pre-existing neutralizing antibodies against Reo.

To explore how these neutralizing antibodies affect Reo efficacy, the researchers developed a mouse model to simulate pre-existing Reo immunity by exposing mice to Reo, thereby inducing neutralizing antibodies, before implanting tumors in the mice. Their findings revealed that neutralizing antibodies significantly reduced the ability of Reo to directly infect pancreatic tumor cells and inhibit tumor growth. However, in mice that lack the ability to produce neutralizing antibodies, Reo showed enhanced tumor control.

Interestingly, the neutralizing antibodies did not prevent the virus from inducing a T-cell-mediated immune response in the tumor. This finding is crucial because it suggests that the immune-stimulating properties of Reo can still be harnessed, regardless of the presence of neutralizing antibodies.

The team then tested combination treatments involving Reo and T-cell-based immunotherapies, finding that they were still effective in mice with neutralizing antibodies. Their research highlights that while neutralizing antibodies present a barrier to Reo’s direct oncolytic action, they do not diminish its ability to prime the immune system.

The study advocates for the strategic use of Reo as part of a multi-faceted immunotherapeutic approach, also in those with high levels of neutralizing antibodies. Given that clinically manufactured Reo has already demonstrated safety in patients, future clinical studies should focus on refining immunotherapy combination strategies.

In summary, van Montfoort and her team have underscored the potential of combining oncolytic viruses with other immune-based treatments, paving the way for more effective and durable cancer therapies.