Marcela Diaz-Montero, PhD

Lerner Research Institute


Karen and Paul Dolan VeloSano Pilot Award

Cell Therapy for Triple Negative Breast Cancer Utilizing Reprogrammed T Lymphocytes

Triple negative breast cancer (TNBC) remains the deadliest form of breast cancer. While recent approval of immune checkpoint inhibitors (ICIs) for TNBC is encouraging and highlights a significant potential for immune-based interventions, ICI is effective in only 20% of TNBC patients, emphasizing a critical need for alternative immune-based treatment modalities. Our studies are aimed at developing a novel immunotherapy for TNBC that involves redirecting the specificity of T cells towards a tumor-specific antigen. This is accomplished by inserting the sequences of target antigen recognizing- T cell receptors (TCRs) into killer T cells. Since TCRs are employed by T cells to recognize their cell targets, expression of antigen-specific TCRs will redirect T cell specificity towards target cells expressing that antigen. We will use α-lactalbumin as the tumor target because it is normally produced during late pregnancy and lactation, but also by aggressive TNBC tumors. This tissue-restricted expression of α-lactalbumin results in a unique availability of reactive T cells. Our laboratory has successfully identified α-lactalbumin reactive human T cells, and we propose to utilize these reactive T cells to extract their TCR sequences and to construct an expression vector, allowing these TCRs to be transferred to T cells from TNBC patients. These engineered T cells will then be able to recognize and kill α-lactalbumin expressing TNBC tumor cells. Our results will provide the basis for a clinical trial in TNBC patients and will also lay groundwork to study the function of engineered T cells to improve their efficacy and minimize potential toxicities.


The goal of my study is to provide a treatment alternative for patients with triple negative breast cancer since there are very few available. We want to devise a way to improve the function of cells that go inside the tumor and kill it.