Exosome Interactions in Acute Lymphocytic Leukemia
Open Access
- Author:
- Spadt, Lauren
- Area of Honors:
- Biomedical Engineering
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Cheng Dong, Thesis Supervisor
Jian Yang, Thesis Honors Advisor - Keywords:
- exosomes
leukemia
CAR-T
flow cytometry - Abstract:
- Acute lymphocytic leukemia (ALL) is a pre-B cell malignancy characterized by rapid disease progression. To combat this disease’s poor prognosis, innovative therapies are currently being developed. Cell-based therapy, like chimeric antigen receptor (CAR)-T cell immunotherapy, modifies patients’ own T cell receptors to specifically attack cancer-specific antigens and spare non-cancerous cells. Rather than focusing solely on cell surface biomarkers, the current antigens targeted by most CAR-T cell immunotherapies, this project seeks to explore the insight given by exosomes. Exosomes, extracellular microvesicles with a size of 30-150 nm, are key players in extracellular communication, including tumor formation and metastasis [1]. Exosomes are abundantly distributed in the bodily fluids, with an average of around 10^11 exosomes (as compared to 10^7 leukocytes) per mL of blood [1,2]. Thus, it was hypothesized that exosome surface biomarkers’ concentration gradients could lead CAR-T cells to cancerous cells. Past research has determined that CAR-T cells produce their own exosomes with significant therapeutic effects, but the interaction of cancer-derived exosomes with CAR-T cells and their associated exosomes is not yet well understood [3]. This research focused on comparing the surface biomarker expression of CD44, CD47, and CD19 on cancerous and non-cancerous cells and their associated exosomes. CD44 expression was lowered in cancerous vs. non-cancerous cells and their associated exosomes, so it is not recommended as a CAR-T cell target. CD47 was identified as a cell surface biomarker for ALL, indicating that it has the potential to be a CAR-T therapy target. Finally, the CD19 expression results validate the current CAR-T therapies that target CD19 antigens, and they also indicate that exosome surfaces have more differential expression of CD19 than cell surfaces [4].