Periodic Reporting for period 4 - RARITY (RAtional design of canceR ImmunoTherapY: one size does not fit all)
Periodo di rendicontazione: 2024-06-01 al 2024-11-30
Cancer is the second most common cause of death worldwide, responsible for nearly 10 million deaths every year. Worryingly, some types of cancer are becoming more common, especially among younger people. This means that the impact of cancer on our society—and our healthcare systems—is enormous and growing. That’s why there is an urgent need for better treatments.
Immunotherapy, which helps the body’s own immune system fight cancer, has become a major part of modern cancer treatment. In recent years, it has transformed the outlook for people with aggressive cancers—such as advanced lung cancer and melanoma—that were once considered untreatable. These therapies work by teaching the immune system how to find and destroy cancer cells.
However, current immunotherapies do not work for everyone. Many patients still do not respond to these treatments and have limited options. The good news is that researchers are continuing to uncover new ways the immune system can be used to fight cancer. These discoveries open up promising paths toward more effective treatments in the future.
RARITY's goal is to find new and better ways to use the immune system to treat cancer—especially for people who do not benefit from existing immunotherapies. The project focuses on three main goals:
1) Using patients’ own immune cells (called T cells) to help fight their cancer.
2) Finding new targets on cancer cells that the immune system can attack.
3) Discovering new types of immune cells that could be used to treat cancer.
In short, RARITY is working to expand the number of tools that can be used to help the immune system fight cancer. By doing so, the project hopes to make immunotherapy more effective—and more available—for the treatment of cancer.
Immunotherapy, which helps the body’s own immune system fight cancer, has become a major part of modern cancer treatment. In recent years, it has transformed the outlook for people with aggressive cancers—such as advanced lung cancer and melanoma—that were once considered untreatable. These therapies work by teaching the immune system how to find and destroy cancer cells.
However, current immunotherapies do not work for everyone. Many patients still do not respond to these treatments and have limited options. The good news is that researchers are continuing to uncover new ways the immune system can be used to fight cancer. These discoveries open up promising paths toward more effective treatments in the future.
RARITY's goal is to find new and better ways to use the immune system to treat cancer—especially for people who do not benefit from existing immunotherapies. The project focuses on three main goals:
1) Using patients’ own immune cells (called T cells) to help fight their cancer.
2) Finding new targets on cancer cells that the immune system can attack.
3) Discovering new types of immune cells that could be used to treat cancer.
In short, RARITY is working to expand the number of tools that can be used to help the immune system fight cancer. By doing so, the project hopes to make immunotherapy more effective—and more available—for the treatment of cancer.
As part of RARITY’s first aim, we set out to develop advanced T cell therapies by identifying, isolating, and converting cancer-specific T cells from patients into high-quality therapeutic products. A key step in this process is identifying markers—specific proteins on the surface of cells—that allow us to distinguish cancer-fighting T cells from the broader population of T cells. Recently, we identified two such markers that can pinpoint T cells with anti-cancer potential in patients with colorectal cancer (van den Bulk et al., JITC 2023). This discovery is a critical step toward developing more effective T cell-based immunotherapies.
For the project’s second aim, we used advanced genomic techniques to identify new targets on cancer cells—molecules that could serve as signals for the immune system to attack. While most current immunotherapies focus on a limited set of such targets, our work has revealed several previously overlooked molecules that could serve as targets for immune-based therapies. We are now validating these findings in additional patient samples to assess their broader significance.
In the third aim, we focused on uncovering lesser-known immune cell populations that may play important roles in fighting cancer. Excitingly, we discovered that a unique type of immune cell known as gamma-delta T cells can recognize cancers that have evaded detection by conventional T cells. Our research also suggests that gamma-delta T cells may contribute to the success of cancer immunotherapy in some patients (de Vries et al., Nature 2023). These groundbreaking findings open up new possibilities for using gamma-delta T cells as powerful tools in future cancer treatments.
RARITY has also played a key role in supporting the development of several technological and analytical approaches for the analysis of cancer tissues. These advances have enabled our group, as well as others, to push forward knowledge in cancer immunology and immunotherapy (e.g. Ijsselsteijn et al., Nature Methods, 2024).
In addition, RARITY has facilitated the initiation of numerous collaborations with fundamental, translational, and clinical scientists. The work carried out within this project has been featured in more than 20 peer-reviewed publications and presented in numerous communications at international conferences.
For the project’s second aim, we used advanced genomic techniques to identify new targets on cancer cells—molecules that could serve as signals for the immune system to attack. While most current immunotherapies focus on a limited set of such targets, our work has revealed several previously overlooked molecules that could serve as targets for immune-based therapies. We are now validating these findings in additional patient samples to assess their broader significance.
In the third aim, we focused on uncovering lesser-known immune cell populations that may play important roles in fighting cancer. Excitingly, we discovered that a unique type of immune cell known as gamma-delta T cells can recognize cancers that have evaded detection by conventional T cells. Our research also suggests that gamma-delta T cells may contribute to the success of cancer immunotherapy in some patients (de Vries et al., Nature 2023). These groundbreaking findings open up new possibilities for using gamma-delta T cells as powerful tools in future cancer treatments.
RARITY has also played a key role in supporting the development of several technological and analytical approaches for the analysis of cancer tissues. These advances have enabled our group, as well as others, to push forward knowledge in cancer immunology and immunotherapy (e.g. Ijsselsteijn et al., Nature Methods, 2024).
In addition, RARITY has facilitated the initiation of numerous collaborations with fundamental, translational, and clinical scientists. The work carried out within this project has been featured in more than 20 peer-reviewed publications and presented in numerous communications at international conferences.
In summary, this project has delivered, beyond the state of the art, (1) specific markers that can be used to isolate T cells with optimal anti-cancer activity for reconversion into high-quality T cell products, (2) promising clues regarding novel targets that can be used to stimulate immune responses against cancer cells and, (3) the demonstration and discovery, for the first time, that gamma-delta T cells are involved in the response to immune checkpoint blockade therapies in a specific population of (colorectal) cancer patients. All of the previous findings will make a contribution to move the field of cancer immunotherapy beyond the state-of-the-art.
The project has also opened new questions for the field, including:
- How to optimally manipulate T cell in vitro to preserve their functional characteristics?
- How to reliably identify unconventional antigens/proteins in cancer cells that can be targeted in the context of immunotherapy?
- What is the role of additional immune cell subsets that have been identified by our project as being involved in anti-cancer immune responses (beyond gamma-delta T cells).
The project has also opened new questions for the field, including:
- How to optimally manipulate T cell in vitro to preserve their functional characteristics?
- How to reliably identify unconventional antigens/proteins in cancer cells that can be targeted in the context of immunotherapy?
- What is the role of additional immune cell subsets that have been identified by our project as being involved in anti-cancer immune responses (beyond gamma-delta T cells).