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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.

Artikel i vetenskaplig tidskrift
Författare Annie George Chandy
Merja Nurkkala
Agnetha Josefsson
Kristina Eriksson
Publicerad i Vaccine
Volym 25
Nummer/häfte 32
Sidor 6037-46
ISSN 0264-410X
Publiceringsår 2007
Publicerad vid Institutionen för biomedicin, avdelningen för patologi
Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning
Sidor 6037-46
Språk en
Länkar dx.doi.org/10.1016/j.vaccine.2007.0...
Ämnesord Animals, Antigens, Viral, immunology, CD8-Positive T-Lymphocytes, immunology, Cancer Vaccines, immunology, Cell Line, Tumor, Chemokines, CC, metabolism, Cholera Toxin, immunology, CpG Islands, immunology, Dendritic Cells, immunology, Female, Histocompatibility Antigens Class II, immunology, Human papillomavirus 16, Immunotherapy, Macrophage Inflammatory Protein-1, metabolism, Mice, Mice, Inbred C57BL, Neoplasms, Experimental, immunology, metabolism, virology, Papillomavirus Infections, immunology, prevention & control, virology, Papillomavirus Vaccines, immunology, RANTES, metabolism, Time Factors, Tumor Virus Infections, immunology, prevention & control, virology
Ämneskategorier Mikrobiologi inom det medicinska området

Sammanfattning

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.

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