Induction of T cell-mediated immunity using a c-Myb DNA vaccine in a mouse model of colon cancer
Benjamin B Williams, Meg Wall, Rebecca Yu Miao, Brenda Williams, Ivan Bertoncello, Michael H Kershaw, Theo Mantamadiotis, Michelle Haber, Murray D Norris, Anand Gautam, Phillip K Darcy, Robert G Ramsay
CANCER IMMUNOLOGY IMMUNOTHERAPY | SPRINGER | Published : 2008
Overexpression of the proto-oncogene c-Myb occurs in more than 80% of colorectal cancer (CRC) and is associated with aggressive disease and poor prognosis. To test c-Myb as a therapeutic target in CRC we devised a DNA fusion vaccine to generate an anti-CRC immune response. c-Myb, like many tumor antigens, is weakly immunogenic as it is a "self" antigen and subject to tolerance. To break tolerance, a DNA fusion vaccine was generated comprising wild-type c-Myb cDNA flanked by two potent Th epitopes derived from tetanus toxin. Vaccination was performed targeting a highly aggressive, weakly immunogenic, subcutaneous, syngeneic, colon adenocarcinoma cell line MC38 which highly expresses c-Myb. Pr..View full abstract
The authors acknowledge and thank the following people for their expert critical input and technical assistance without whom this work would have not been possible; Sally Lightowler, Dr. Jordane Malaterre, Seb Dworkin, Dani Cardozo, Kym Stanley, Mira Liu, Carol Van Puyenbroek, Ralph Rossi, Dr. Jeremy Swann and Duy Huynh. The National Health and Medical Research Council have supported this work and RGR and PKD are the recipients of NHMRC Research Fellowships from this organization.