Scientists have reported new information about how anti-CD20 antibodies trigger the immune system to attack tumour cells.
Anti-CD20 antibodies, such as rituximab, are used in clinical practice to treat patients with B-cell lymphoma. The scientists from the Institut Pasteur in Paris, France, used in vivo imaging to watch the action of the antibodies in real time in B-cell lymphoma cells. They did so by genetically engineering tumour cells to produce a fluorescent dye which changed colour as they were destroyed.
This showed that macrophage cells play a crucial role by surrounding and ingesting the tumour cells that were coated with the injected antibodies. Findings were published in the journal Science Advances recently.
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Lead author, Dr Capucine Grandjean, said: “What surprised us was the observation that this elimination phase, which begins immediately after the injection of the antibody, became less effective after just a few hours.” This was despite there still being enough anti-CD20 antibodies available to bind to tumour cells.
The team also discovered that the macrophages in the tumour are unlikely to have the ability to destroy all of the cancer cells. They hope these findings on the weaknesses of antibody therapy “will open new avenues for the development of next-generation therapies”.
“In particular,” they write, “increasing the presence and activity of macrophages in the tumour represents a promising strategy to boost the efficacy of these therapeutic antibodies.”
Grandjean CL, Garcia Z, Lemaître F, Bréart B, Bousso P. (2021) “Imaging the mechanisms of anti-CD20 therapy in vivo uncovers spatiotemporal bottlenecks in antibody-dependent phagocytosis.” Science Advances, doi: 10.1126/sciadv.abd6167
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