Can Viruses Help Treat Cancer?

Summary

New research published in Nature suggests that genetic remnants from ancient viral infections, known as endogenous retroviruses (ERVs), influence the effectiveness of immunotherapy in lung cancer patients. Antibodies targeting ERV-encoded proteins may enhance the immune response to cancer, with 45% of patients showing a positive reaction to immunotherapy. This discovery could pave the way for developing vaccines that boost antibody production at tumor sites, potentially improving immunotherapy outcomes. Additionally, oncolytic viruses are being explored as a novel class of cancer therapy, with the potential to directly kill tumor cells or stimulate antitumor immunity.

Takeaways

• 🧬 Genetic elements from ancient viral infections may influence the response to immunotherapy in cancer patients.
• 💉 Immunotherapy, particularly immune checkpoint blockade (ICB), uses the body's immune system to fight cancer by inhibiting checkpoint proteins like PD-1 and PD-L1.
• 🔍 ICB is not universally effective, with about 70% of lung cancer patients not responding to the therapy, and the reasons behind this are not fully understood.
• 🦠 B cells and the antibodies they produce are implicated in the response to ICB, with B cell expansion around tumors potentially predicting a positive response to checkpoint inhibition.
• 🐁 In a mouse model of lung adenocarcinoma, ICB treatment promoted survival and increased anti-tumor antibodies, some of which target endogenous retroviruses (ERVs).
• 🌐 ERVs are remnants of retroviruses that infected our ancestors and are now part of the human genome, with over 8% of it composed of retroviral sequences.
• 🛡️ ERVs do not typically encode infectious viral particles but can produce viral-like proteins, and they are upregulated in cancer tissues, making them targets for antibodies.
• 🏥 Research suggests that anti-ERV antibodies are key in anti-tumor immunity and may enhance the effectiveness of ICB treatment in lung cancer.
• 🧬 The study indicates that ERVs could 'trick' the immune system into recognizing tumor cells as infected, thus activating an immune response to eliminate them.
• 🧬 Human patient samples showed a correlation between the presence of anti-ERV antibodies and a positive response to ICB, as well as better overall survival rates.
• 🛑 Oncolytic viruses (OVs) are a new class of cancer therapy that can kill tumor cells or induce antitumor immunity, and their use is being explored for more effective delivery methods.
• 🧬 The concept of using cells as carriers for the delivery of OVs by integrating viral genetic material into the human genome is a promising area of research.

Q & A

Why do some cancer patients respond to immunotherapy while others do not?

The script suggests that genetic elements from ancient viral infections, known as endogenous retroviruses (ERVs), may influence the response to immunotherapy. Antibodies targeting proteins encoded by these sequences could enhance the effectiveness of immunotherapy in lung cancer patients.

What is immune checkpoint blockade (ICB) and how does it work?

ICB is a cancer treatment method that leverages the body's immune system to fight cancer. It works by inhibiting interactions between checkpoint proteins, such as PD-1 and PD-L1, on T cells and other cells. This prevents the 'off' signal from being sent to T cells, allowing them to remain active and destroy tumor cells.

What is the problem with the effectiveness of ICB treatment?

Approximately 70% of lung cancer patients do not respond to ICB treatment. The exact reasons for this are not fully understood, but the script suggests that B cells and the antibodies they produce may be related to the response to ICB.

What role do B cells play in the response to checkpoint blockade?

B cell expansion in tissue around tumors can be used to predict whether a tumor will respond positively to checkpoint inhibition. The antibodies produced by B cells, particularly those targeting antigens expressed by tumors, can flag cancer cells for destruction by immune cells.

What are endogenous retroviruses (ERVs) and why are they significant in this study?

ERVs are DNA remnants of retroviruses that infected our ancestors thousands or millions of years ago. They are significant because the study found that antibodies targeting ERV glycoproteins are key players in anti-tumor immunity and responses to ICB treatment.

How does the expression of ERVs in cancer tissues relate to the immune response?

ERVs are generally upregulated in cancer tissues compared to healthy cells. The study suggests that the expression of ERV glycoproteins in mouse cancer cells and the presence of anti-ERV antibodies can help prolong survival and contribute to the success of ICB treatment.

What is the potential application of ERVs in cancer treatment according to the study's findings?

The study suggests that developing cancer treatment vaccines comprised of ERV genes could boost antibody production at a patient's cancer site, potentially improving immunotherapy outcomes.

What are oncolytic viruses (OVs) and how do they contribute to cancer therapy?

Oncolytic viruses are a new class of cancer therapy that can directly kill or lyse tumor cells or induce antitumor immunity. They are engineered to enhance immune stimulation and/or remove pathogenicity-associated genes.

What challenges are associated with the administration of oncolytic virus therapeutics?

Challenges include inefficient targeting of tumor sites, the risk of cytokine storm, and the difficulty of administering OVs via the most desirable route, intravenous delivery, to reach both primary and metastasized tumors.

What is the novel approach proposed by researchers in the Journal of Virology to address the challenges of OV administration?

Researchers propose using cells as carriers for the systematic delivery of OVs by integrating cDNA from an oncolytic coxsackievirus into the genome of human cells, allowing for the production and release of viral particles potentially at the tumor site.

What do the findings of the study and the report in the Journal of Virology suggest about the role of viruses in cancer immunity and therapeutics?

The findings suggest that viruses and their integrated genetic material play a significant role in cancer immunity and therapeutics, both through the immune response triggered by ERVs and the direct action of oncolytic viruses in killing tumor cells and modulating immune responses.