Lentivector immunization stimulates potent CD8 T cell responses against melanoma self-antigen tyrosinase-related protein 1 and generates antitumor immunity in mice

Yanjun Liu, Yibing Peng, Michael Mi, Jose Guevara-Patino, David H Munn, Ning Fu, Yukai He

Research output: Contribution to journalArticle

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Abstract

Recombinant lentivector immunization has been demonstrated to induce potent CD8 T cell responses in vivo. In this study, we investigated whether lentivector delivering a self/tumor Ag, tyrosinase related protein 1 (TRP1), could stimulate effective antitumor T cell responses. We found that immunization with lentivector expressing mutated TRP1 Ag elicited potent CD8 T cell responses against multiple TRP1 epitopes. Importantly, the activated CD8 T cells effectively recognize wild-type TRP1 epitopes. At peak times, as many as 10% of CD8 T cells were effector cells against TRP1 Ag. These cells killed wild-type TRP1 peptide-pulsed target cells in vivo and produced IFN-γ after ex vivo stimulation. The CD8 T cell responses were long-lasting (3-4 wk). Immunized mice were protected from B16 tumor cell challenge. In a therapeutic setting, lentivector immunization induced potent CD8 T cell responses in tumor bearing mice. The number of infiltrating T cells and the ratio of CD8/CD4 were dramatically increased in the tumors of immunized mice. The tumor-infiltrating CD8 T cells were functional and produced IFN-γ. The potent CD8 T cell responses stimulated by lentivector immunization eliminated small 3-day s.c. B16 tumors and strongly inhibited the growth of more established 5-day tumors. These studies demonstrate that genetic immunization with lentivector expressing mutated self/tumor Ag can generate potent CD8 T cell immune responses and antitumor immunity that prevent and inhibit B16 tumor growth, suggesting that lentivector immunization has the potential for tumor immunotherapy and immune prevention.

Original languageEnglish (US)
Pages (from-to)5960-5969
Number of pages10
JournalJournal of Immunology
Volume182
Issue number10
DOIs
StatePublished - May 15 2009

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Melanoma-Specific Antigens
Autoantigens
Immunity
Immunization
T-Lymphocytes
Neoplasms
Epitopes
tyrosinase-related protein-1
CD4-CD8 Ratio
Growth
Immunotherapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Lentivector immunization stimulates potent CD8 T cell responses against melanoma self-antigen tyrosinase-related protein 1 and generates antitumor immunity in mice. / Liu, Yanjun; Peng, Yibing; Mi, Michael; Guevara-Patino, Jose; Munn, David H; Fu, Ning; He, Yukai.

In: Journal of Immunology, Vol. 182, No. 10, 15.05.2009, p. 5960-5969.

Research output: Contribution to journalArticle

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