CD4-dependent potentiation of a high molecular weight-melanoma-associated antigen-specific CTL response elicited in HLA-A2/Kb transgenic mice

Liaomin Peng, Eric Ko, Wei Luo, Xinhui Wang, Protul A. Shrikant, Soldano Ferrone

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

The human high m.w.-melanoma-associated Ag (HMW-MAA) is an attractive target for the immunotherapy of melanoma, due to its relatively high expression in a high percentage of melanoma lesions and its restricted distribution in normal tissues. Active immunization with HMW-MAA mimics has been previously shown to induce a HMW-MAA-specific, T cell-dependent Ab response associated with an apparent clinically beneficial effect in advanced melanoma patients. Although T cells play an important role in controlling tumor growth, only limited information is available to date about the induction of HMW-MAA-specific CTL. In this report, we show that immunization of HLA-A2/Kb transgenic mice with HMW-MAA cDNA-transfected syngeneic dendritic cells elicited a CD8+ CTL response specific for HMW-MAA peptides with HLA-A2 Ag-binding motifs. The elicited CTL lysed HLA-A2+HMW-MAA+ melanoma cells in vitro, and mouse HLA-A2/Kb cells pulsed with HMW-MAA-derived peptides in vitro and in vivo. Although this CTL response could be generated in the absence of CD4+ T cell help, harnessing CD4 + T cell help in a noncognate Ag-specific manner with the polyclonal activator staphylococcal enterotoxin A augmented the CTL response. These results imply that dendritic cell-based immunization, in combination with CD4 + T cell help, represents an effective strategy to implement T cell-based immunotherapy targeting HMW-MAA in patients with HMW-MAA-bearing tumors.

Original languageEnglish (US)
Pages (from-to)2307-2315
Number of pages9
JournalJournal of Immunology
Volume176
Issue number4
DOIs
StatePublished - Feb 15 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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