Activating anti-CD40 antibodies induce tumour invasion by cytotoxic T-lymphocytes and inhibition of tumour growth in experimental liver cancer.
The aim of this study was to investigate the effects of an activating anti-CD40 antibody (aCD40Ab) on leukocyte adhesion to tumour vessels, leukocyte migration and tumour growth in experimental liver cancer. Morris-Hepatoma was induced by subcapsular inoculation of tumour cells in the liver of ACI-rats. On day 7 and 8 after tumour cell injection, one group of the animals received aCD40Ab. On day 13 the tumour volume was measured and intravital microscopy was performed quantifying leukocyte adherence in the liver. Furthermore, immunohistological analyses were performed. aCD40Ab-Treated animals showed increased leukocyte-endothelium interaction, demonstrated substantially more T- and natural killer (NK) cells in the tumour and had a distinctly decreased tumour volume. Our results show that treatment with aCD40Ab stimulates endothelial leukocyte adhesion in tumour vessels and migration of CD4 cells/CD8 T-cells and NK cells into the tumour and inhibits tumour growth. Thus, the CD40/CD154 pathway is a worthwhile target for adjuvant immunotherapy.
Department of General Surgery, University of Heidelberg, Im Neunenheimer Feld 110, 69120 Heidelberg, Germany.
Eduard
E
Ryschich
Angela
A
Märten
Eduard
E
Schmidt
Michael
M
Linnebacher
Nicolas
N
Wentzensen
Sven
S
Eisold
Ernst
E
Klar
Markus W
MW
Büchler
Jan
J
Schmidt
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000917:Antibody Formation; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D019013:CD40 Antigens / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D045744:Cell Line, Tumor; D007167:Immunotherapy / Q000379:methods; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008297:Male; D009368:Neoplasm Transplantation; D051381:Rats; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*
D000906:Antibodies; D019013:CD40 Antigens