Date of Award
January 2023
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Biomedical Sciences
First Advisor
David S. Bradley
Abstract
Immunotherapies now stand at the forefront of cancer treatment as a versatile arsenal of cutting-edge tools wielded by medical professionals to combat and conquer a spectrum of formidable diseases. Most notably, immunotherapies such as immune checkpoint inhibitors, have revolutionized the field of oncology offering a promising alternative to conventional treatments like chemo and radiation therapy with significant improvements for patients in terms of quality of life and survival. Immunotherapies can be uniquely personalized to a patient's genetic and immune system profile leading to more effective treatments and durable long-lasting responses. Our research group has identified Staphylococcal enterotoxin I as a potent T cell activator that drives multifaceted antitumor responses but has not been incorporated into the arsenal due to the risk of HLA-associated toxicity. The following work aims to understand further and reduce that risk. HLA-DQ8 mice with established B16-F10 tumors receiving 25µg of SEI on days 6 and 9 post-tumor implant resulted in an astonishing 100% progression-free survival for greater than 400 days. However, SEI cancer immunotherapy was not successful in HLA-DR3 humanized transgenic or allogenic C57BL/6 mice. Furthermore, HLA-DQ8 mice rechallenged with 2.5x105 live B16-F10 cells experienced 100% survival for greater than 100 days post-implant. However, SEI immunotherapy was only limitedly effective against established Lewis lung carcinoma and did not provide cross-protection against rechallenge with either LLC or TC-1 tumor cell lines. The studies presented herein demonstrate that single superantigen SEI immunotherapy elicits antitumor responses against melanoma and supports further investigation into clinical applications of superantigen-based immunotherapies.
Recommended Citation
Velaris, Nathan, "Staphylococcal Enterotoxin I Immunotherapy Combined With HLA-DQ8 Induces Tumoricidal Activity, With Low Superantigen Toxicity, Leading To Long-Term Survival And Tumor-Specific Memory Against Established B16-F10 Melanoma In Humanized HLA-DQ8 Transgenic Mice" (2023). Theses and Dissertations. 5710.
https://commons.und.edu/theses/5710