Author ORCID Identifier
0000-0003-4888-7862
Date of Graduation
5-2017
Document Type
Dissertation (PhD)
Program Affiliation
Immunology
Degree Name
Doctor of Philosophy (PhD)
Advisor/Committee Chair
Willem W. Overwijk
Committee Member
Gregory A. Lizee
Committee Member
Pierre D. McCrea
Committee Member
Jagannadha K. Sastry
Committee Member
Stephen E. Ullrich
Abstract
Despite remarkable progresses in vaccinology, therapeutic cancer vaccines have not achieved their full potential. We previously showed that the duration of antigen presentation critically affected the quantity and quality of T cell response and subsequent anti‐tumor efficacy. Here we describe L‐tyrosine amino acid‐based microparticles as a novel peptide vaccine adjuvant for the induction of tumor‐specific T cells. L‐tyrosine microparticles did not induce inflammasome activation, but instead extended antigen presentation time. The consequent prolongation in antigen presentation translated into prolonged T cell proliferation and superior numbers and anti‐tumor function of vaccination‐induced CD8+ T cells. Indeed, prolonging antigen presentation by repeated injection of peptide in saline resulted in an increase in T cell numbers similar to that observed after vaccination with peptide/L‐tyrosine microparticles. These results suggest that the duration of antigen presentation is critical for optimal induction of anti‐tumor T cells, and can be manipulated through proper vaccine formulation.
Keywords
adjuvant, CD8 T cell, cancer, vaccine, pmel-1, B16 melanoma, L-tyrosine