Lung Cancer Research Progress
2023–2025 Peg’s Fight for Life Research Award Recipient
Principal Investigator: Anastasios Dimou, MD, Mayo Clinic College of Medicine
Project Title: BiTE to target EGFR peptide: HLA class I complexes in EGFR mutant lung cancers
Immunotherapy has transformed treatment for many people with lung cancer, but patients with EGFR-mutated non-small cell lung cancer (NSCLC) often do not benefit from current immune checkpoint inhibitors. Dr. Anastasios Dimou, recipient of the 2023–2025 Peg’s Fight for Life Research Award, is working to change that. His project is focused on developing a highly targeted immunotherapy approach that helps the immune system recognize and attack EGFR-mutant lung cancer cells more effectively.
Meet Dr. Anastasios Dimou
Dr. Dimou earned his M.D. from the University of Athens Medical School, where he first developed his interest in lung cancer research. He went on to complete advanced medical and research training at leading institutions across the United States, including:
- A postdoctoral fellowship at the Yale University School of Medicine
- A residency in Internal Medicine at Albert Einstein Medical Center
- A Hematology/Oncology Fellowship at the Medical University of South Carolina
- An advanced fellowship in Investigational Cancer Therapeutic Thoracic Oncology at the University of Colorado
Dr. Dimou’s dedication to translational cancer research has already earned national recognition. In 2018, he received the Travel Award for Advanced Course in Basic and Clinical Immunology from the Federation of Clinical Immunology Society. That same year, he was awarded the AACR-Conquer Cancer Foundation of ASCO Young Investigator Award for Translational Cancer Research, helping lay the foundation for the work now supported by A Breath of Hope.
Today, Dr. Dimou is continuing that work with the goal of overcoming resistance to immunotherapy in EGFR-driven and other mutation-driven lung cancers.
About the Project
A New Immunotherapy Strategy for EGFR-Mutant Lung Cancer
The EGFR gene provides instructions for making the epidermal growth factor receptor, a protein involved in cell growth and survival. When EGFR is mutated, it can drive uncontrolled cell growth and lead to lung cancer. While targeted therapies have improved outcomes for many patients with EGFR mutations, immunotherapy has remained much less effective in this group.
Dr. Dimou’s project is based on an important idea: in some patients, the immune system can actually recognize EGFR mutations as “non-self.” His team is working to harness that response by developing a Bispecific T-cell Engager (BiTE) — a type of engineered therapy designed to connect T cells directly to cancer cells carrying EGFR mutations.
To do this, the project is:
- Screening antibody libraries to identify antibodies that bind selectively to mutant EGFR targets
- Distinguishing mutated EGFR targets from normal EGFR to reduce off-target effects
- Building a BiTE-based therapy that can redirect immune cells against EGFR-mutant lung cancer
- Testing these candidates in laboratory models before future preclinical development
The long-term goal is to create a more personalized immunotherapy strategy for patients with EGFR-mutant lung cancer.
Final Progress Report
In this phase of the project, Dr. Dimou’s team has made meaningful technical progress toward identifying antibody candidates that could form the basis of a future BiTE therapy.
They have:
- Created stable target and control molecular complexes representing mutant EGFR peptides presented with HLA molecules, which are necessary for screening highly specific antibodies
- Selected promising EGFR mutation and HLA combinations most likely to form stable complexes for successful screening
- Identified lung cancer cell lines with the relevant EGFR mutation and HLA-A*11:01 pairing for future cellular testing
- Conducted multiple rounds of phage display screening to search for antibody sequences that bind the cancer target more strongly than control targets
- Shifted to a yeast display strategy to improve selection specificity after early screening attempts produced non-specific binding
- Identified three candidate antibody sequences that showed stronger binding to the EGFR-mutant target than the control, although some control binding remains and further refinement is needed
As a next step, the team plans to convert these candidates into IgG1 antibodies, label them with fluorophores, and test whether they can bind selectively to EGFR-mutant lung cancer cells while sparing control cells.
These findings represent important progress in a technically challenging area of research and move the project closer to a new therapeutic strategy for EGFR-mutant lung cancer.
Why This Matters
Patients with EGFR-mutant lung cancer often face a major gap in treatment options when standard immunotherapy does not work. Dr. Dimou’s work addresses that unmet need by developing a therapy designed specifically for the unique biology of these tumors.
This research could:
- Open the door to new immunotherapy strategies for EGFR-mutant lung cancer
- Improve the precision of treatment by targeting mutation-specific tumor markers
- Help overcome one of the biggest challenges in lung cancer care: immunotherapy resistance
- Support the development of more personalized therapies for patients with mutation-driven NSCLC
The Peg’s Fight for Life Award is helping advance this innovative work and bringing new hope to patients and families affected by lung cancer.
The Peg’s Fight for Life Award is helping advance this innovative work and bringing new hope to patients and families affected by lung cancer.
