TY - JOUR
T1 - CD4-dependent potentiation of a high molecular weight-melanoma-associated antigen-specific CTL response elicited in HLA-A2/Kb transgenic mice
AU - Peng, Liaomin
AU - Ko, Eric
AU - Luo, Wei
AU - Wang, Xinhui
AU - Shrikant, Protul A.
AU - Ferrone, Soldano
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2006/2/15
Y1 - 2006/2/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=32044474901&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=32044474901&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.176.4.2307
DO - 10.4049/jimmunol.176.4.2307
M3 - Article
C2 - 16455987
AN - SCOPUS:32044474901
SN - 0022-1767
VL - 176
SP - 2307
EP - 2315
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -