Journal
JOURNAL OF IMMUNOLOGY
Volume 200, Issue 10, Pages 3464-3474Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1700467
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Funding
- Cancer Prevention Research Institute of Texas Individual Investigator Research Award [RP140522]
- Vietnam Education Foundation fellowship
- National Cancer Institute T32 Training Grant [CA009599]
- Cancer Prevention Research Institute of Texas Training Grant [RP140106]
- National Cancer Institute Cancer Center Support Grant [P30CA16672]
- Cancer Prevention Research Institute of Texas Grant [RP130397]
- National Institutes of Health High-End Instrument Grant [1S10OD012304-01]
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Despite remarkable progresses in vaccinology, therapeutic cancer vaccines have not achieved their full potential. We previously showed that an excessively long duration of Ag presentation critically reduced the quantity and quality of vaccination-induced T cell responses and subsequent antitumor efficacy. In this study, using a murine model and tumor cell lines, we studied L-tyrosine amino acid-based microparticles as a peptide vaccine adjuvant with a short-term Ag depot function for the induction of tumor-specific T cells. L-Tyrosine microparticles did not induce dendritic cell maturation, and their adjuvant activity was not mediated by inflammasome activation. Instead, prolonged Ag presentation in vivo translated into increased numbers and antitumor activity of vaccination-induced CD8(+) T cells. Indeed, prolonging Ag 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. Our results show that the duration of Ag presentation is critical for optimal induction of antitumor T cells, and can be manipulated through vaccine formulation.
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