Cancer Immunotherapy: Targeting Tumor Cells’ ‘Guards’ Shows Promise in Lung & Ovarian Cancer
Researchers at the Icahn School of Medicine at Mount Sinai are pioneering a novel immunotherapy approach to combat metastatic cancer. This experimental treatment differs from conventional methods by focusing not on the cancer cells themselves, but on the cells that shield and support them.
A New Strategy for Advanced Cancers
The findings, published in the January 22 online issue of Cancer Cell, a Cell Press Journal, detail successful testing of this strategy in preclinical models of aggressive metastatic ovarian and lung cancers. This research suggests a potential breakthrough for advanced solid tumors that have proven resistant to existing therapies.
Inspired by the Trojan Horse
The approach draws inspiration from the ancient tale of the Trojan horse. Instead of attempting to directly penetrate the tumor, the therapy aims to enter by targeting macrophages – immune cells that normally act as guardians for cancer cells. By disabling these protective cells, the treatment intends to open the tumor to immune system attack, ultimately leading to cancer cell destruction.
Tumors create a “walled fortress,” as described by lead study author Jaime Mateus-Tique, PhD, a faculty member in Immunology and Immunotherapy at the Icahn School of Medicine at Mount Sinai. Current immunotherapies often struggle to overcome this protective barrier. The team’s strategy aims to convert these “guards” into allies, creating a pathway for a powerful immune response within the tumor.
How Macrophages Aid Cancer
Tumor-associated macrophages, while beneficial in healthy tissue for fighting infection and repairing damage, are reprogrammed within tumors. This reprogramming allows them to suppress immune responses, promote cancer growth, and facilitate the spread of the disease. The Mount Sinai team developed a therapy designed to selectively remove these tumor macrophages while preserving healthy ones, shifting the tumor environment from immune-suppressed to immune-active.
Re-Engineering Immune Cells
The therapy utilizes CAR T cells, which are engineered immune cells created from a patient’s own T cells. Traditionally, CAR T cell treatments target and kill cancer cells directly. However, identifying suitable targets on solid tumors has been challenging. To address this, the researchers redirected the CAR T cells to recognize tumor macrophages instead.
The engineered CAR T cells were also modified to release interleukin-12, a molecule that stimulates the activity of killer T cells. In mice with metastatic lung and ovarian cancer, treatment with these cells resulted in significantly prolonged survival, with many animals experiencing complete remission.
Reshaping the Tumor Landscape
Advanced spatial genomics techniques were used to analyze how the therapy impacted the tumor environment. These analyses revealed that the treatment successfully removed immune-suppressing cells and attracted immune cells capable of killing cancer. This shift is particularly noteworthy because it makes the therapy ‘antigen-independent,’ meaning it doesn’t rely on identifying specific markers on cancer cells. This could broaden the therapy’s applicability to a wider range of cancers, including those unresponsive to traditional immunotherapy.
“Macrophages are found in every type of tumor, sometimes outnumbering the cancer cells,” explains senior author Brian Brown, PhD, Director of the Icahn Genomics Institute, Vice Chair of Immunology and Immunotherapy, Associate Director of the Marc and Jennifer Lipschultz Precision Immunology Institute, and Mount Sinai Professor of Genetic Engineering, at the Icahn School of Medicine at Mount Sinai. “Our treatment converts these cells from protecting the cancer to killing it.”
Looking Ahead
The researchers emphasize that human studies are necessary to determine the safety and effectiveness of this therapy. The current results are considered proof of concept, not a definitive cure. The team is currently focused on refining the approach, specifically controlling the release of interleukin-12 within tumors in mouse models to maximize impact and ensure safety as they move toward potential human testing. They believe this strategy could serve as a foundation for future CAR T therapies that target the support cells surrounding tumors, rather than the cancer cells themselves.
Frequently Asked Questions
What is the main goal of this new immunotherapy?
The main goal is to target the cells surrounding and protecting cancer cells – tumor-associated macrophages – rather than attacking the cancer cells directly.
In what types of cancer was this therapy tested?
This strategy was tested in aggressive preclinical models of metastatic ovarian and lung cancer.
Is this therapy ready for use in humans?
No, the researchers emphasize that studies in humans are still needed to determine the safety and effectiveness of the therapy.
Given the potential to reshape the tumor environment and overcome resistance to existing treatments, how might this approach influence the future of cancer immunotherapy?