Therapeutic dendritic cell vaccination with Ag coupled to cholera toxin in combination with intratumoural CpG injection leads to complete tumour eradication in mice bearing HPV 16 expressing tumours.
We have evaluated whether cholera toxin (CT) can enhance the efficiency of therapeutic dendritic cell (DC) vaccination in mice bearing a human papilloma virus (HPV) 16 antigen (Ag) expressing tumour. Mice were therefore injected with the TC-1 cancer cell line expressing E6 and E7, which are the major oncogenic proteins produced in HPV-induced cervical cancer, and they were then vaccinated with Ag pulsed DCs. While vaccination with E7 pulsed DCs had no impact on tumour growth, DCs pulsed with CT conjugated E7 (CT-E7) significantly reduced tumour size. However, this treatment was only able to eradicate the tumour in 11% of the affected animals. For complete tumour eradication, combinational therapy with CT-E7 pulsed DCs and local treatment of the tumour with CpG oligodeoxynucleotides (CpG) was required. Combinational therapy was associated with increased expression of MHC I and MHC II and increased levels of chemokine production in the tumour. These results suggest that combined treatment with CT-Ag pulsed DCs and local CpG administration offers an efficient strategy to eradicate an already existing HPV-E7 expressing tumour in mice.
Chandy
Annie George
AG
Department of Rheumatology and Inflammation Research, Gothenburg University, Guldhedsgatan 10A, 413 46 Gothenburg, Sweden. annie.george.chandy@microbio.gu.se
Nurkkala
Merja
M
Josefsson
Agnetha
A
Eriksson
Kristina
K
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism; D002772:Cholera Toxin / Q000276:immunology*; D018899:CpG Islands / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D052162:Human papillomavirus 16; D007167:Immunotherapy; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D030361:Papillomavirus Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D053918:Papillomavirus Vaccines / Q000276:immunology; D013997:Time Factors; D014412:Tumor Virus Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology
D000956:Antigens, Viral; D019496:Cancer Vaccines; C496534:Ccl3 protein, mouse; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC; D000949:Histocompatibility Antigens Class II; D019402:Macrophage Inflammatory Proteins; D053918:Papillomavirus Vaccines; D002772:Cholera Toxin