Lentivector immunization induces tumor antigen-specific B and T cell responses in vivo Journal Article
| Authors: | Casado, J. G.; Janda, J.; Wei, J.; Chapatte, L.; Colombetti, S.; Alves, P.; Ritter, G.; Ayyoub, M.; Valmori, D.; Chen, W.; Lévy, F. |
| Article Title: | Lentivector immunization induces tumor antigen-specific B and T cell responses in vivo |
| Abstract: | Expression of the cancer/germ-line antigen NY-ESO-1 by tumors elicits spontaneous humoral and cellular immune responses in some cancer patients. Development of vaccines capable of stimulating such comprehensive immune responses is desirable. We have produced recombinant lentivectors directing the intracellular synthesis of NY-ESO-1 (rLV/ESO) and have analyzed the in vivo immune response elicited by this vector. Single injection of rLV/ESO into HLA-A2-transgenic mice elicited long-lasting B and T cell responses against NY-ESO-1. CD8+ T cells against the HLA-A2-restricted peptide NY-ESO-1157-165 were readily detectable ex vivo and showed restricted TCR Vβ usage. Moreover, rLV/ESO elicited a far greater anti-NY-ESO-1157-165 CD8+ T cell response than peptide- or protein-based vaccines. Anti-NY-ESO-1 antibodies were rapidly induced after immunization and their detection preceded that of the antigen-specific CD8+ T cells. The rLV/ESO also induced CD4+ T cells. These cells played an essential role as their depletion completely abrogated B cell and CD8+ T cell responses against NY-ESO-1. The induced CD4+ T cells were primarily directed against a single NY-ESO-1 epitope spanning amino acids 81-100. Altogether, our study shows that rLV/ESO induces potent and comprehensive immune responses in vivo. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. |
| Keywords: | controlled study; unclassified drug; nonhuman; antigen expression; cd8+ t lymphocyte; cd8-positive t-lymphocytes; animal cell; mouse; animal; metabolism; animals; mice; animal experiment; membrane proteins; in vivo study; drug potency; tumor antigen; b lymphocyte; transgenic mouse; gene vector; b-lymphocytes; genetic vectors; mice, transgenic; t lymphocyte receptor; blood; immunology; lymphocyte activation; cellular immunity; antigens, neoplasm; gamma interferon; immunoglobulin g; cancer vaccine; cancer vaccines; ny eso 1 antigen; antibody response; cancer immunization; cd4+ t lymphocyte; cd4-positive t-lymphocytes; recombinant proteins; ctag1b protein, human; membrane protein; recombinant protein; drug response; vaccines, synthetic; lentivirus; lentivirus vector; single drug dose; tumor immunity; cytokine production; immunophenotyping; virus recombinant; t cell depletion; hermes antigen; ex vivo study; humoral immunity; antibodies, neoplasm; t lymphocyte activation; lymphocyte antigen receptor; drug administration route; recombinant vaccine; lentivirinae; nonviral gene delivery system; immunization; hla a2 antigen; cancer antibody; ny-eso-1; tumor immunology; receptors, antigen, b-cell; l selectin; interleukin 7 receptor; b cell response; lentivector; t cell response; ny eso 1 antigen [151-165]; t lymphocyte receptor v beta |
| Journal Title: | European Journal of Immunology |
| Volume: | 38 |
| Issue: | 7 |
| ISSN: | 0014-2980 |
| Publisher: | Wiley V C H Verlag Gmbh |
| Date Published: | 2008-07-01 |
| Start Page: | 1867 |
| End Page: | 1876 |
| Language: | English |
| DOI: | 10.1002/eji.200737923 |
| PUBMED: | 18546142 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 12" - "Export Date: 17 November 2011" - "CODEN: EJIMA" - "Source: Scopus" |
