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

Available for download on Saturday, May 05, 2018

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