TY - JOUR
T1 - Class II-transfected tumor cells directly present endogenous antigen to CD4+ T cells in vitro and are APCs for tumor-encoded antigens in vivo
AU - Armstrong, Todd D.
AU - Clements, Virginia K.
AU - Ostrand-Rosenberg, Suzanne
PY - 1998
Y1 - 1998
N2 - We have previously demonstrated that class II-transfected tumor cells are very effective immunogens that protect against wild-type primary and metastatic tumor and, if supertransfected with genes encoding co-stimulatory molecules, are immuno-therapeutic agents that successfully treat mice with established solid tumor. These results are consistent with our hypothesis that the class II-transfected tumor cells act as antigen-presenting cells (APCs) that directly activate tumor-specific CD4+ T cells; however, direct data supporting this hypothesis are lacking. In the present study, we test this hypothesis using class II-transfected tumor cells supertransfected with the hen egg lysozyme gene as a surrogate tumor antigen. In vitro antigen presentation assays demonstrate that class II-transfected tumor cells present to CD4+ T cells endogenously encoded tumor antigen, provided they do not co-express the class II-associated invariant chain. In vivo experiments using genetically marked tumor cells and host APCs demonstrate that both class II-transfected tumor cells and host cells are APCs for tumor-encoded antigens, although tumor cells appear to dominate the response. These results support the hypothesis that the immunogenicity and therapeutic value of class II-transfected tumor cells stem from their ability to function as APCs for tumor-encoded antigens and directly activate tumor-specific CD4+ T lymphocytes.
AB - We have previously demonstrated that class II-transfected tumor cells are very effective immunogens that protect against wild-type primary and metastatic tumor and, if supertransfected with genes encoding co-stimulatory molecules, are immuno-therapeutic agents that successfully treat mice with established solid tumor. These results are consistent with our hypothesis that the class II-transfected tumor cells act as antigen-presenting cells (APCs) that directly activate tumor-specific CD4+ T cells; however, direct data supporting this hypothesis are lacking. In the present study, we test this hypothesis using class II-transfected tumor cells supertransfected with the hen egg lysozyme gene as a surrogate tumor antigen. In vitro antigen presentation assays demonstrate that class II-transfected tumor cells present to CD4+ T cells endogenously encoded tumor antigen, provided they do not co-express the class II-associated invariant chain. In vivo experiments using genetically marked tumor cells and host APCs demonstrate that both class II-transfected tumor cells and host cells are APCs for tumor-encoded antigens, although tumor cells appear to dominate the response. These results support the hypothesis that the immunogenicity and therapeutic value of class II-transfected tumor cells stem from their ability to function as APCs for tumor-encoded antigens and directly activate tumor-specific CD4+ T lymphocytes.
KW - Antigen presentation
KW - CD4 T cells
KW - Major histocompatibility complex class II
KW - Tumor immunity
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UR - http://www.scopus.com/inward/citedby.url?scp=0031898594&partnerID=8YFLogxK
U2 - 10.1097/00002371-199805000-00008
DO - 10.1097/00002371-199805000-00008
M3 - Article
C2 - 9610914
AN - SCOPUS:0031898594
SN - 1524-9557
VL - 21
SP - 218
EP - 224
JO - Journal of Immunotherapy
JF - Journal of Immunotherapy
IS - 3
ER -