Project title: Deciphering novel neoantigen landscape and vaccine targets in pancreatic neuroendocrine neoplasms
Anguraj Sadanandam, PhD The Institute of Cancer Research
- Status: Completed
- Year(s): 2023
- Grant Type: Pilot
- Research Type: Translational
- Primary Tumor Site: Pancreas
Project Description:
Dr. Sadanandam’s research aims to improve treatment for pancreatic neuroendocrine neoplasms (PanNENs), especially the aggressive subtype, by addressing the limited effectiveness of current therapies, including immune checkpoint treatment.
What critical NET problem will you try to solve through your research?
The urgency stems from PanNENs’ resistance to standard therapies due to their heterogeneity. The proposed solution involves developing a groundbreaking neoantigen-based (abnormal proteins specific to cancer cells) vaccination strategy, offering new hope for patients with aggressive PanNENs when traditional immunotherapy is not feasible.
Why is this important?
Understanding and utilizing the body’s immune response against PanNENs is crucial for enhancing patient well-being. Dr. Sadanandam and his team’s research focused on identifying specific neoantigens for personalized immunotherapies not only addresses treatment challenges but also deepens our understanding of PanNENs’ biology and fosters the development of innovative and more effective treatment approaches, potentially transforming the landscape of PanNEN therapy.
What will you do as part of this research project?
Dr. Sadanandam’s research project focuses on deciphering the neoantigen landscape in PanNENs, especially an aggressive subtype, utilizing large data, artificial intelligence-based machine-learning algorithms and cutting-edge techniques. The goal is to identify and validate neoantigens as potential vaccine candidates.
How might your research improve the diagnosis and/or treatment of NETs?
This innovative approach could transform PanNEN therapy, moving away from traditional methods and contributing valuable insights into neuroendocrine tumors, leading to more effective and targeted treatments for PanNENs, potentially improving outcomes and survival rates.
What is your next step?
By integrating cutting-edge technologies and computational methods, Dr. Sadanandam aims to develop a personalized immunotherapy strategy to transform PanNEN treatment, ultimately improving patient outcomes.
Outcomes:
Pancreatic neuroendocrine tumors are rare cancers that can be challenging to treat. One exciting new approach is immunotherapy, which helps the body’s immune system recognize and attack cancer cells. In this project, we focused on finding special markers on tumor cells, called neoantigens. These are small pieces of proteins found only in cancer cells, making them promising targets for personalized cancer vaccines.
We analyzed a large number of tumor samples to identify these unique markers. By studying how genes behave differently in cancer cells, we discovered several new potential neoantigens that are specific to these tumors. This is an important step forward, as it expands the pool of possible targets for future treatments.
We then tested these targets in the lab using immune cells called T cells, which play a key role in fighting cancer. Our results showed that several of the identified neoantigens can successfully attach to immune molecules on the cell surface. This is a critical first step in allowing the immune system to recognize cancer cells.
Our testing system worked very well, with strong responses seen using known control targets. This gives us confidence in our approach and the quality of our findings. While immune activation was limited in healthy donor cells, this is expected at this stage, as these cells have not been previously exposed to tumor-specific targets.
Overall, this project has developed a powerful and reliable pipeline to discover and test new cancer-specific targets. It also highlights the importance of studying these targets in patient-derived immune systems in future work.
In the long term, this research brings us closer to developing personalized cancer vaccines that can train the immune system to better recognize and attack tumors. This could lead to more precise, effective, and less toxic treatment options for patients.
Additional Details
- City: London
- Country: UK
- Grant Duration: 1
- Sponsor: Laura and Lew Moorman
DISCLAIMER
NETRF funds laboratory research to understand the development of neuroendocrine tumors and translational research to explore new concepts in treatment. Research grant descriptions and research updates from NETRF are not intended to serve as medical advice. It can take years for research discoveries to be fully validated and approved for patient care. Always consult your health care providers about your treatment options.