Combining Gene Therapy and Immunotherapy for Advanced Lung Cancer Treatment

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• Suicide Gene Therapy Explained
• Why Viruses Target Cancer
• Gene Therapy Limitations in Lung Cancer
• Mesothelioma Gene Therapy Application
• Immunotherapy and Gene Therapy Combination
• Future of Cancer Combination Therapies

Suicide Gene Therapy Explained

Gene therapy for cancer involves using modified viruses to deliver destructive genetic material directly into tumor cells. Dr. Michael Lanuti, MD, a prominent thoracic surgeon, describes a specific approach known as "suicide gene therapy." This advanced technique utilizes engineered viruses, such as adenovirus or herpes virus, that are altered to be less toxic to healthy human cells. These viral vectors are designed to carry so-called suicide genes into the cancer cell environment.

Once inside the tumor, these genes activate mechanisms that lead to the programmed death of cancer cells. Dr. Lanuti's research, spanning over a decade including a dedicated postdoctoral fellowship, has focused on developing these innovative viral delivery systems to improve lung cancer treatment outcomes, particularly for cases where conventional therapies show limited effectiveness.

Why Viruses Target Cancer

Viruses demonstrate a natural predilection for infecting cancer cells due to the unique biological environment within tumors. Dr. Michael Lanuti, MD, explains that cancer cells divide rapidly, creating ideal conditions for viral replication. This selective replication means that engineered therapeutic viruses can infect and multiply within cancer cells much more efficiently than in normal, healthy cells.

The modified viruses used in gene therapy are specifically designed to exploit this biological vulnerability. While common cold viruses (adenoviruses) have been traditional vectors, more recent research has explored herpes viruses and other viral platforms. This targeted approach allows for concentrated therapeutic action at the tumor site while minimizing damage to surrounding healthy tissue, a significant advantage in cancer treatment.

Gene Therapy Limitations in Lung Cancer

Despite promising research developments, lung cancer presents particular challenges for gene therapy applications. Dr. Michael Lanuti, MD, notes that while experimental models show tumors can be "knocked down" by gene therapy, complete cures remain elusive. The complex nature of lung cancer tumors, often with diffuse spread and difficult-to-reach locations, limits the effectiveness of viral delivery systems that work best on localized tumors.

Dr. Michael Lanuti, MD, explains that many successful gene therapy models involve direct injection into easily accessible tumors, an approach less feasible for deep-seated lung malignancies. This delivery challenge has prompted researchers to explore alternative administration methods, including intravenous delivery and inhalation techniques, though these present their own set of obstacles in ensuring sufficient viral concentration reaches the tumor sites.

Mesothelioma Gene Therapy Application

Malignant pleural mesothelioma, a rare cancer often linked to asbestos exposure, represents a particularly promising application for gene therapy. Dr. Michael Lanuti, MD, identifies this aggressive cancer as especially conducive to viral gene therapy approaches due to its anatomical location and growth pattern. Mesothelioma typically forms as a fibrous tumor along the lung's lining, making complete surgical removal extremely challenging.

Even with advanced surgical techniques, surgeons often leave behind microscopic tumor cells after debulking procedures. Dr. Lanuti describes a potential solution where surgeons could "wash the chest" with a therapeutic virus containing suicide genes after resection. This approach would target residual cancer cells directly at the surgical site, addressing the critical problem of local recurrence that often limits long-term survival in mesothelioma patients.

Immunotherapy and Gene Therapy Combination

The most significant advancement in cancer gene therapy involves strategic combination with immunotherapy, creating a powerful synergistic treatment approach. Dr. Michael Lanuti, MD, explains that while the virus destroys tumor cells directly through suicide gene mechanisms, it simultaneously exposes tumor antigens to the immune system. This dual action helps the immune system recognize cancer cells as foreign invaders, effectively priming it for a targeted attack.

This combination approach addresses a fundamental challenge in cancer treatment: many tumors develop mechanisms to hide from the immune system. By using viral gene therapy to break apart tumor cells, the resulting cellular debris provides the necessary signals to activate immune responses. Dr. Michael Lanuti, MD, emphasizes that this combined strategy often proves more effective than single-agent therapies, leveraging the strengths of both treatment modalities for improved patient outcomes.

Future of Cancer Combination Therapies

The integration of gene therapy with immunotherapy represents the next wave of innovation in cancer treatment. Dr. Michael Lanuti, MD, identifies this combination approach as particularly promising given immunotherapy's current status as "the hottest topic in cancer biology." Research across multiple laboratories is demonstrating encouraging results with these combined modalities, suggesting a new paradigm for treating advanced cancers.

This research direction acknowledges that complex diseases like lung cancer and mesothelioma rarely respond optimally to single-mechanism treatments. As Dr. Lanuti concludes, the future of cancer therapy lies in harnessing complementary approaches that attack tumors through multiple pathways simultaneously. These combination strategies offer hope for improved survival rates and better quality of life for patients with advanced thoracic malignancies that have traditionally had limited treatment options.

Full Transcript

Dr. Anton Titov, MD: Prominent lung cancer surgeon and gene therapy and immunotherapy expert explains progress and future in precision medicine lung tumor treatment. Leading lung cancer surgeon explains lung cancer treatment gene therapy. Does immunotherapy and gene therapy work for stage 4 lung cancer? There is a new immunotherapy for lung cancer stage 3 that can increase survival.

Dr. Anton Titov, MD: Gene therapy for lung cancer is one of your interests. You did a lot of research and a postdoctoral fellowship on lung cancer gene therapy. You published a virus-based approach to gene therapy for lung cancer. This is a very interesting modality of action.

Dr. Anton Titov, MD: Could you please talk about your research in gene therapy for lung cancer?

Dr. Michael Lanuti, MD: Yes. So my interest in lung cancer gene therapy has gone back now more than a decade. I did it in surgical training. And gene therapy in general is still finding its niche in cancer therapy. Lung cancer itself is not the best cancer to treat with gene therapy.

Dr. Anton Titov, MD: Why? Gene cancer therapy. What is gene therapy and viral gene therapy?

Dr. Michael Lanuti, MD: We're trying to identify something that can get to the cancer tissue and destroy it. And it's something that you would either inject, ingest, or put in the bloodstream. Many gene therapy models are tumors that are local. We used to use such gene therapy models. We would inject tumors with viruses.

For example, we would inject a modified virus, either a common cold virus, adenovirus or, more recently, a herpes virus. And those viruses would be manipulated. We have to make them less toxic to make you sick. But also we would put in suicide genes in viruses to help destroy tumor cells. The word that we use is "suicide gene therapy".

Dr. Anton Titov, MD: Why do we use viruses?

Dr. Michael Lanuti, MD: Viruses tend to replicate better in cancer cells that are dividing quickly. Viruses replicate more in cancer cells than in your native cells. So there's a predilection for infection of cancer cells. And so in the models that we've used, we've had some cancer treatment improvement. The tumors do get knocked down by gene therapy. We don't necessarily cure tumors with cancer gene therapy.

So what I see is gene therapy in the future would be this. There are some tumors that are more conducive to gene therapy. It could be a tumor that is related to asbestos. It's called mesothelioma. It is a very fibrous tumor along the edge of the lung. Surgeons are only so good at the debriding or debulking of mesothelioma. Surgeons are good at partial resection of mesothelioma. And there's often tumor cells left behind.

That's where we think maybe cancer gene therapy would help. You "wash the chest" with a virus that contains a suicide gene. I think the newest iteration of gene therapy is going to be now a combination with immunotherapy.

Dr. Anton Titov, MD: Immunotherapy will stimulate the immune system to recognize tumor.

Dr. Michael Lanuti, MD: Then we use the virus to destroy tumor. And you expose the tumor to the immune system as you destroy tumor with virus. So that the immune system recognizes non-self. Immune system then gets activated up by cancer immunotherapy.

Clearly, the combination therapy often works in many diseases better than a single-agent therapy. So in that sense combination of the cancer gene therapy with the cancer immunotherapy is better.

Dr. Anton Titov, MD: Yes, so it's under investigation now, including many labs, and some are showing good results. And the cancer immunotherapy is the hottest topic there is in cancer biology.

Dr. Michael Lanuti, MD: And so I think it should be harnessed. So the next wave of cancer gene therapy would be a combination therapy with cancer immunotherapy.