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

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/K(b) 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/K(b) 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.

• Authors: Liaomin Peng, Eric Ko, Wei Luo, Xinhui Wang, Protul A Shrikant, Soldano Ferrone
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 176 Issue 4 Pg. 2307-15 (Feb 15 2006) ISSN: 0022-1767 [Print] United States
• PMID: 16455987 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Antigens, Differentiation, T-Lymphocyte
• Antigens, Neoplasm
• CD4 Antigens
• CD69 antigen
• Enterotoxins
• HLA-A2 Antigen
• HMW-MAA
• Lectins, C-Type
• enterotoxin A, Staphylococcal
• Interferon-gamma

Topics

• Animals
• Antigens, CD (metabolism)
• Antigens, Differentiation, T-Lymphocyte (metabolism)
• Antigens, Neoplasm (immunology)
• CD4 Antigens (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• Cell Line
• Dendritic Cells (immunology, metabolism)
• Enterotoxins (pharmacology)
• HLA-A2 Antigen (immunology)
• Humans
• Immunization
• Interferon-gamma (biosynthesis)
• Lectins, C-Type
• Lymphocyte Activation (drug effects)
• Mice
• Mice, Transgenic
• T-Lymphocytes, Cytotoxic (drug effects, immunology)
• Up-Regulation