Unlocking New Therapeutic Approaches for Brain Metastases
Melanoma that has spread to the brain presents a formidable challenge in cancer treatment owing to its resistance to most systemic drugs. However, a team of scientists from Brigham and Women’s Hospital has developed a new immunotherapeutic approach that leverages a twin stem cell model to effectively target metastatic melanomas in the brain. Their strategy combines the release of a virus that kills cancer cells (oncolytic) with the delivery of immunomodulators that enhance the immune system’s ability to fight cancer. Using CRISPR/Cas9 gene editing, they created a second stem cell model that ensures the oncolytic virus does not attack the cells that release it. Thus, their approach amplifies the release of the virus and strengthens the immune system’s response to the disease.
The twin stem cell model effectively activates immune responses in mice models, showing great promise in reducing tumor growth and extending survival. In particular, the models accurately mimic human environments, boosting the efficacy of the therapy for a Phase I trial. The team validated the approach for melanoma with leptomeningeal metastasis, though they believe the technique can be applied to other types of cancer such as breast and lung cancer. Intrathecal injection, the delivery method for twin stem cells, is a technique already used in the treatment of other diseases and is more sustainable than other immunotherapies that require repeated administrations. The team plans to launch a Phase I trial soon to establish the therapy’s efficacy.
Expanding the Scope of Immunotherapy for Brain Metastases
The twin stem cell model represents a significant breakthrough in cancer treatment, offering hope to patients with limited therapeutic options. More importantly, it highlights the potential to merge multiple therapeutic approaches to combat resistant cancers and improve patient response. The approach can be applied to other types of brain metastases and even other types of cancer, affording renewed hope to patients with advanced-stage diseases.
Immunotherapy has emerged as a promising treatment option for cancer, with several clinical trials currently underway to establish the efficacy of different approaches. While the results of the trials are mixed, the field has seen significant progress in the past few years, primarily driven by technological advancements such as gene editing and molecular biology. These developments have enabled researchers to understand the mechanisms of the immune system better and how it can be leveraged to fight cancer more effectively.
Immunotherapy also presents several advantages over traditional chemotherapy and radiation therapy, such as precise targeting, fewer off-target effects, and more durable responses. However, it also poses unique challenges, such as the potential for autoimmune reactions, patient heterogeneity, and delayed or insufficient responses. Thus, there is a need to develop methods that enhance the immune system’s response to cancer and improve the safety and efficacy of immunotherapies.
Advancing the Frontiers of Cancer Research and Treatment
The twin stem cell model is a testament to the significant strides made in cancer research and treatment. The approach leverages the twin stem cells to overcome obstacles such as the limited efficacy of systemic drugs and the vulnerability of cells that release oncolytic viruses. By combining different therapeutic approaches such as gene editing, molecular biology, and immunotherapy, the researchers were able to develop a therapy that offers more sustainable and effective treatment options for melanoma patients.
The twin stem cell model also underscores the need for more comprehensive preclinical testing, which accurately mimics real-world patient responses to therapy. The models explored in this study show promise and can enhance the success of Phase I trials, which often fail due to inaccurate preclinical models. Thus, investing in more representative preclinical models can improve the success rates of clinical trials and ensure patients get access to more effective therapies.
In conclusion, the twin stem cell model revolutionizes brain metastases treatment and offers hope to patients with advanced-stage melanoma. The approach highlights the potential of integrating different therapeutic methods to combat resistant cancers and underscores the need for comprehensive preclinical models to improve clinical trial success rates. As the field of cancer research advances, it is essential to explore novel approaches such as the twin stem cell model to improve patient outcomes and bring better therapies to market.
Summary:
Scientists at Brigham and Women’s Hospital have developed a new immunotherapeutic approach that leverages a twin stem cell model to effectively target metastatic melanomas in the brain. Their strategy combines the release of a virus that kills cancer cells (oncolytic) with the delivery of immunomodulators that enhance the immune system’s ability to fight cancer. The twin stem cell model effectively activates immune responses in mice models, showing great promise in reducing tumor growth and extending survival. The approach can be applied to other types of brain metastases and other types of cancer, affording hope to patients with advanced-stage diseases.
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Acting as a team, the twin stem cells activate the immune system to suppress tumor growth and prolong survival in representative preclinical models.
Overall survival for patients with melanoma that has spread to the brain is only four to six months. Immunotherapies, which harness the power of the immune system to attack cancer cells, have generated excitement in recent years for their potential to revolutionize the treatment of metastatic melanomas, but the results of early clinical trials indicate that the outlook for most of patients is still bad. Now, scientists at Brigham and Women’s Hospital, a founding member of the Mass General Brigham health care system, have integrated multiple therapeutic approaches to more effectively target melanoma in the brain. In preclinical studies, the scientists successfully activated immune responses in sophisticated mouse models that mimic human environments. The findings are published in Science Translational Medicine.
“We know that in advanced cancer patients with brain metastases, systemic drugs, given intravenously and orally, do not effectively target brain metastases,” said corresponding author Khalid Shah, MS, PhD, director of the Center for Immunotherapy Translational and Stem Cell Therapy (CSTI). ) and vice chair for research in the Department of Neurosurgery at Brigham and faculty at Harvard Medical School and the Harvard Stem Cell Institute (HSCI). “We have now developed a new immunotherapeutic approach that is sustainable and delivered locally to the tumor. We believe that locally delivered immunotherapies represent the future of how we will treat brain metastases.”
The therapy designed by the scientists uses a “twin stem cell model” designed to maximize an attack on cancer cells that have spread to a part of the brain known as the leptomeninges. A stem cell releases a virus that kills cancer (oncolytic), a strategy that has previously shown promise in reducing tumor growth. Using stem cells to deliver the virus increases the amount of virus that can be released and ensures that circulating antibodies do not break down the virus before it is released in cancer cells.
However, the oncolytic virus also destroys the very cells that release it, making it an untenable therapeutic option on its own. So the scientists used CRISPR/Cas9 gene editing to create a second stem cell that cannot be attacked by the oncolytic virus and instead releases proteins (immunomodulators) that strengthen the immune system to help fight the virus. cancer.
Twin stem cells can be delivered by intrathecal injection, a technique already used in the treatment of other diseases. Unlike other immunotherapies that have emerged in recent years, it does not need to be administered repeatedly. The authors emphasize that this approach can be used in other cancers with brain metastases, such as lung and breast cancer, and they are working to design similar treatments for these cancers.
In particular, the authors were able to design a preclinical mouse model that closely represents a human model of melanoma with leptomeningeal metastasis, which they used to test their therapy. They found that the therapy successfully activated immune responses in their models that mimic human responses, improving the likelihood that the therapy would succeed in a Phase I trial, which the authors hope to launch in the near future.
“Several biologic therapies that show promise often fail in Phase I or Phase II clinical trials, in part because preclinical models do not authentically replicate clinical settings,” Shah said. “We realized that if we didn’t fix this piece of the puzzle, we would always be catching up. I don’t think we’ve gotten to a point in the last 20 years where we’ve come as close to curing brain metastases as we are.” now”.
https://www.sciencedaily.com/releases/2023/05/230531150214.htm
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