Antibody-targeted NY-ESO-1 to mannose receptor or DEC-205 in vitro elicits dual human CD8+ and CD4+ T cell responses with broad antigen specificity Journal Article
| Authors: | Tsuji, T.; Matsuzaki, J.; Kelly, M. P.; Ramakrishna, V.; Vitale, L.; He, L. Z.; Keler, T.; Odunsi, K.; Old, L. J.; Ritter, G.; Gnjatic, S. |
| Article Title: | Antibody-targeted NY-ESO-1 to mannose receptor or DEC-205 in vitro elicits dual human CD8+ and CD4+ T cell responses with broad antigen specificity |
| Abstract: | Immunization of cancer patients with vaccines containing full-length tumor Ags aims to elicit specific Abs and both CD4+ and CD8+ T cells. Vaccination with protein Ags, however, often elicits only CD4+ T cell responses without inducing Ag-specific CD8+ T cells, as exogenous protein is primarily presented to CD4+ T cells. Recent data revealed that Ab-mediated targeting of protein Ags to cell surface receptors on dendritic cells could enhance the induction of both CD4+ and CD8+ T cells. We investigated in this study if these observations were applicable to NY-ESO-1, a cancer-testis Ag widely used in clinical cancer vaccine trials. We generated two novel targeting proteins consisting of the full-length NY-ESO-1 fused to the C terminus of two human mAbs against the human mannose receptor and DEC-205, both internalizing molecules expressed on APC. These targeting proteins were evaluated for their ability to activate NY-ESO-1-specific human CD4+ and CD8+ T cells in vitro. Both targeted NY-ESO-1 proteins rapidly bound to their respective targets on APC. Whereas nontargeted and Ab-targeted NY-ESO-1 proteins similarly activated CD4+ T cells, cross-presentation to CD8+ T cells was only efficiently induced by targeted NY-ESO-1. In addition, both mannose receptor and DEC-205 targeting elicited specific CD4+ and CD8+ T cells from PBLs of cancer patients. Receptor-specific delivery of NY-ESO-1 to APC appears to be a promising vaccination strategy to efficiently generate integrated and broad Ag-specific immune responses against NY-ESO-1 in cancer patients. Copyright © 2011 by The American Association of Immunologists, Inc. |
| Journal Title: | Journal of Immunology |
| Volume: | 186 |
| Issue: | 2 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2011-01-15 |
| Start Page: | 1218 |
| End Page: | 1227 |
| Language: | English |
| DOI: | 10.4049/jimmunol.1000808 |
| PROVIDER: | scopus |
| PUBMED: | 21149605 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 4 March 2011" - "CODEN: JOIMA" - "Source: Scopus" |
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