As the second anniversary of the Covid-19 pandemic approaches, the variant of the virus has made daily headlines, and we all have a deep understanding of the damage the virus can cause. They invade our bodies and communities and can subvert our world. However, as “virus” and “vaccine” have now become part of our daily lives and vocabulary, we should not ignore the reverse potential of viruses and their ability to treat the most challenging diseases.
Although conceptually counterintuitive, this approach is not new.Stimulated by repeated observations of tumor regression after natural virus infection in the past century, Researchers have made progress in using the natural or engineering capabilities of viruses to infect, replicate, and destroy tumor cells without damaging healthy cells—for example, using herpes to treat melanoma. Initially, we thought that this direct cancer-killing effect was the main mechanism of action. Therefore, these viruses were called “oncolytic viruses”, essentially acting as self-amplifying cytotoxic agents. Today, we know that this is just one aspect of the power of these viruses.
Create anti-cancer virus
Cancer cells have evolved survival mechanisms that can fly under the radar of the immune system. Compared with healthy cells, their immunogenicity is relatively small. However, oncolytic viruses have the ability to make it easier for the immune system to see tumors and mark the area of attack. It is this anti-tumor immune activation that may induce a long-term response in patients. In the past two decades, immunotherapy has revolutionized cancer treatment, and viruses are well suited to further increase its impact. Therefore, oncolytic virus is one of the most exciting emerging treatments. With their good safety, clinical efficacy evidence and low production costs, they are expected to improve patient care with wide accessibility.
The typical process of designing viral therapies for cancer treatment requires the selection of virus species that are harmless to humans, or, more commonly, the engineering of pathogenic viruses to make them safe for use by ensuring that they selectively infect cancer cells rather than healthy cells. This process usually reduces the immunostimulatory efficacy of the virus, which in turn is compensated by transgene expression. In addition, cancer is not a panacea. It is a challenge for drug developers. It is necessary to find the most effective virus for a specific tumor type and make the discovery of oncolytic viruses a time-consuming and resource-intensive one. work.
Fortunately, emerging platform technologies allow us to select, rationally design, and optimize existing viruses that specifically target tumors of interest, sometimes even avoiding the need for transgene expression. These innovative methods help accelerate the discovery of new viral therapeutics for cancer types with high unmet needs.
Use flu to fight breast cancer
One of these diseases is breast cancer, the second leading cause of death in women. Only in 2020, More than 2 million patients worldwide Was diagnosed with this disease. It is also one of the most difficult cancers to treat with immunotherapy, mainly due to the heterogeneity of breast cancer subtypes and the low visibility of the immune system. As we innovate to improve the prognosis of these patients, influenza viruses may provide some answers. In fact, the same characteristics of influenza that are so unwelcome—its powerful infection and ability to stimulate a powerful immune response—make it an ideal viral therapy candidate for cancer. Influenza virus particles include molecules that recognize specific glycosylation patterns that are up-regulated on the surface of breast cancer cells so that they can be targeted preferentially to trigger an anti-cancer immune response. If the patient has had the flu or vaccinated against the flu in the past, their original immunity may allow them to take the lead in fighting the disease, because immune memory cells can quickly recognize the virus and improve the cross-priming of antiviral drugs. -Tumor response.
But how can we prevent the patient from catching the flu Give the patient a cold? The answer lies in the attenuation of the virus.
Using the genetic code to develop better treatments
One way to unlock the great potential of viruses as anticancer agents is codon deoptimization. This artificial intelligence-assisted method systematically exchanges hundreds of codons in the viral genome with less commonly used codons in human cells. This slows down the translation speed of the virus and prevents the virus from effectively replicating in healthy cells, while retaining all the outward immune stimulating characteristics of the original virus. For viruses that target cancer, the optimization of attenuation provides higher safety, because the re-encoded viruses can still selectively replicate in tumor cells, and these tumor cells have shut down their innate immune response and cellular use. Other mechanisms to stop the virus infection.
Importantly, the codon modification produces a genetically stable phenotype that cannot be restored to a more infectious form and is compatible with the efficient, large-scale manufacturing of the selected cell line. By using this method and combining it with other emerging or mature technologies, we can expand viral therapy to more patients and increase the effectiveness of other treatment modalities as part of a rationally designed joint program.
This technology not only leads to a flu-based breast cancer therapy, but also applies to other virus-tumor pairs, bringing us one step closer to maximizing the transformational potential of cancer immunotherapy.
As we continue to fight Covid-19, the peak of the flu season is approaching, let this be an encouraging reminder of the possible benefits of the virus that we are often afraid of.
Photo: Main_sail, Getty Images
