Baylor College of Medicine
PROJECT
Engineering a Precision T Cell Therapy for Breast Cancer
ROLE
Summer Research Intern
TIMELINE
Summer 2021 (CAGT Summer Internship Program)
TEAM
Hoyos Lab, Baylor College of Medicine. Mentor: Paul Shafer, PhD. PI: Valentina Hoyos, MD. Funded by Susan G. Komen and the Baylor Breast SPORE.
Susan G. Komen, Baylor Specialized Program of Research Excellence (SPORE)
Funding
Triple-negative breast cancer, hormone receptor-positive (HR+) breast cancer
Disease Area
Dr. Paul Shafer, PhD
Mentor
Dr. Valentina Hoyos Velez, MD
Principal Investigatior
01 Summary
I researched an engineered T cell receptor (TCR) therapy targeting neoantigens specific to HR+ metastatic breast cancer, an approach designed to avoid the off-tumor toxicity risk of standard tumor-associated antigen targeting.
CORE COMPETENCIES:
Experimental Design, Molecular Biology Techniques, Data Analysis, Scientific Communication
02 Approach
I used an antigen-specific T cell pipeline to generate neoantigen-reactive T cell lines from patient and donor samples, then isolated single neoantigen-specific clones through IFNγ capture and limiting dilution. I cloned the TCR alpha and beta chains from these clones via 5' RACE and sequencing, then assembled them into an SFG retroviral vector construct for expression testing in producer cells.
03 Impact
I◊I identified and validated two neoantigen-specific TCR clones, targeting the Y537S and R248W driver mutations, establishing candidate TCR sequences for a future engineered T cell therapy platform in metastatic breast cancer. This work laid early groundwork for a precision immunotherapy approach in a patient population with limited targeted treatment options.
