Document Detail


Lentivector immunization stimulates potent CD8 T cell responses against melanoma self-antigen tyrosinase-related protein 1 and generates antitumor immunity in mice.
MedLine Citation:
PMID:  19414747     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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-gamma 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-gamma. 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.
Authors:
Yanjun Liu; Yibing Peng; Michael Mi; Jose Guevara-Patino; David H Munn; Ning Fu; Yukai He
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  182     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-05     Completed Date:  2009-05-26     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5960-9     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, Neoplasm / genetics,  immunology*
Autoantigens / genetics,  immunology
CD8-Positive T-Lymphocytes / immunology*
Cancer Vaccines / immunology*
Epitopes, T-Lymphocyte / immunology
Flow Cytometry
Fluorescent Antibody Technique
Genetic Vectors / immunology*
Lentivirus / genetics,  immunology
Lymphocytes, Tumor-Infiltrating / immunology
Melanoma, Experimental / immunology*,  therapy
Membrane Glycoproteins / immunology*
Mice
Mutation
Oxidoreductases / immunology*
Grant Support
ID/Acronym/Agency:
R01 CA116444/CA/NCI NIH HHS; R01 CA116444-03/CA/NCI NIH HHS; R01CA16444/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, Neoplasm; 0/Autoantigens; 0/Cancer Vaccines; 0/Epitopes, T-Lymphocyte; 0/Membrane Glycoproteins; EC 1.-/Oxidoreductases; EC 1.14.18.-/Tyrp1 protein, mouse
Comments/Corrections
Erratum In:
J Immunol. 2009 Jul 15;183(2):1496

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