Tumour-inhibitory effects of dendritic cells administered at the site of HPV 16-induced neoplasms.
Experiments were designed to examine whether administration of APC at the site of HPV 16-associated tumours can inhibit tumour growth and whether the efficacy of established dendritic cell lines is comparable to that of fresh BMDC populations. Mice were inoculated s.c. with APC, either bone marrow-derived dendritic cells differentiated in medium supplemented with GM-CSF and IL-4 (BMDC), or with established dendritic cell lines DC2.4 or JAWS II. The pretreated mice, together with untreated controls, were challenged with syngeneic HPV 16-transformed cells MK16 at the site of APC administration. It has been found that both BMDC and dendritic cell lines can inhibit tumour growth and that the efficacy of the established dendritic cell lines DC2.4 and JAWS II was comparable to that of fresh BMDC populations. In vitro induction of proliferative spleen cell responses by co-cultivation with MK16 antigen-pulsed BMDC or MK16 antigen-pulsed dendritic cell lines revealed that both types of APC populations can prime immune reactions directed against syngeneic HPV 16-associated neoplasms. Taken together, the results suggest that local increase in the number of dendritic cells at the site of HPV 16-associated tumours can inhibit progression of the tumours and that the dendritic cell lines which are efficient in this respect can be considered and should be tested in both, preclinical and human systems for delivery of therapeutic vaccines against HPV 16-associated neoplasms.
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague.
L
L
Mendoza
J
J
Bubeník
J
J
Símová
J
J
Korb
J
J
Bieblová
V
V
Vonka
M
M
Indrová
R
R
Mikysková
T
T
Jandlová
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D002469:Cell Separation; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D005434:Flow Cytometry; D016219:Immunotherapy, Adoptive; D051379:Mice; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000628:therapy* / Q000821:virology; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000276:immunology; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000276:immunology