CANCER RESEARCH UK-funded scientists have discovered that linking a molecule which initiates antibody production,to a ‘saboteur’ molecule, triggers the immune system to selectively destroy faulty cells. These findings published in Blood*, could potentially be used to selectively destroy tumour cells while ignoring healthy cells.
Mice were immunised with an antigen linked to a CpG ‘saboteur’ molecule. The antigen smuggled the CpG into specific cells to trigger the immune response system to produce antibodies that could potentially seek and destroy cancer cells.
The scientists demonstrated that mice immunised with different antigen-CpG** complexes had boosted antibody responses when compared with immunisation with the same antigen not linked to CpG. This demonstrated that the antigen was able to sneak CpG into the immune response hub of the cell.
This new strategy could be used for future cancer vaccination strategies – either through preventative medicine or cancer treatment – to stimulate specific immune responses against faulty proteins in tumour cells. The technique in effect supercharges the body’s immune system to help it fight cancer.
Lead author, Dr Facundo Batista, based at Cancer Research UK’s London Research Institute, said: “This technique allows antibodies to be produced to recognise very specific altered proteins in a tumour cell while ignoring the proteins in a healthy cell. This discovery reveals the potential in using the immune system to hunt down and destroy cancer cells. It gives us a route to make treatment as specific as possible.”
Dr Lesley Walker, Cancer Research UK’s director of science information, said: “There have already been exciting preliminary advances in treatment of lymphoma using antibodies which harness the body’s own immune response in a new way.
“This research is an important step in furthering Cancer Research UK’s role at the cutting edge of the development of effective therapies for cancer with fewer unpleasant side effects.”
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*BCR-mediated TLR9 stimulation drives B cell proliferation and formation of antigen-specific plasma cells. Eckl-Dorna and Batista. February 2009. Blood.
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CpG is a tiny saboteur molecule (derived from microbial DNA) which is able to cross a B-cell membrane. Once inside it triggers B cells to produce specialised antibodies by activating an internal receptor called Toll Like Receptor 9 (TLR9).
About antibody production
Antigens are detected by B cells in specialised tissues such as the spleen or lymph nodes – known as secondary lymphoid organs. Antigen-activated B cells can follow two pathways of differentiation. They can either become short-lived plasma cells responsible for rapid production of low-affinity antibodies. Or they can mature into long-lived plasma cells to produce high-affinity antibodies or long-lasting memory cells.
Immunisation with antigen-CpG complexes enhanced specific antibody responses in mice. Antigen and CpG were prepared onto streptavidin polystyrene beads the size of a typical virus. The mice were infected simultaneously with two different antigens. For each group of mice immunised one of the antigens was conjugated with CpG. Fourteen days after administration the production of Ag-specific antibodies was measured using ELISA Enzyme-Linked Immuno Sorbent Assay and showed there was an enhancement in antigen-specific antibody production for the antigen conjugated with CpG.
The antigen-TLR9 agonist complex (ag-CpG) promotes specific B cells to secrete antibodies tailored to destroy a particular antigen. This is in contrast to CpG alone that would trigger the whole population of B cells non-specifically to secrete generic antibodies, which destroy all antigens
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