An anti-ICAM-2 (CD102) monoclonal antibody induces immune-mediated regressions of transplanted ICAM-2-negative colon carcinomas.
Monoclonal antibodies (mAbs) can mediate antitumor effects by indirect mechanisms involving antiangiogenesis and up-regulation of the cellular immune response rather than by direct tumor cell destruction. From mAbs raised by immunization of rats with transformed murine endothelial cells, a mAb (EOL4G8) was selected for its ability to eradicate a fraction of established colon carcinomas that did not express the EOL4G8-recognized antigen. The antigen was found to be ICAM-2 (CD102). Antitumor effects of EOL4G8, which required a functional T-cell compartment, were abrogated by depletion of CD8(+) cells and correlated with antitumor CTL activity, whereas only a mild inhibition of angiogenesis was observed. Interestingly, we found that EOL4G8 acting on endothelial ICAM-2 markedly enhances leukotactic factor activity-1-independent adhesion of immature dendritic cells to endothelium-an effect that is at least in part mediated by DC-SIGN (CD209).
Melero
Ignacio
I
Gene Therapy Unit, Department of Medicine, University of Navarra School of Medicine, C/Irunlarrea, I-31008 Pamplona, Spain. imelero@unav.es
Gabari
Izaskun
I
Corbí
Angel L
AL
Relloso
Miguel
M
Mazzolini
Guillermo
G
Schmitz
Volker
V
Rodriguez-Calvillo
Mercedes
M
Tirapu
Iñigo
I
Camafeita
Emilio
E
Albar
Juan P
JP
Prieto
Jesús
J
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D004727:Endothelium / Q000166:cytology / Q000276:immunology; D005260:Female; D006801:Humans; D037102:Lectins / Q000276:immunology; D037181:Lectins, C-Type; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D011956:Receptors, Cell Surface / Q000276:immunology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D015854:Up-Regulation; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D037102:Lectins; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C065289:ICAM2 protein, human