Platelets carrying immunotherapy antibodies could provide a new and effective way of targeting tumours across the body
Larger tumours are noticeable and are comparatively easy to remove in most cases, but cancers have frequently already established other smaller colonies nearby and across the body by hijacking the circulatory system. Using blood cells, namely platelets, could therefore be a great method of catching stragglers; preventing metastasis and recurrence.
"Our goal was to study a new and effective way to treat cancer patients after they have surgery. There has been tremendous interest in developing new, effective strategies to prevent cancer recurrence after surgery. Among them, cancer immunotherapy has received considerable attention. But immunotherapeutic agents do not directly attack the tumor—they use the body's immune system to kill cancer cells"
A new way
Immunotherapy has typically focused on either delivery antibodies by themselves, or altering immune cells to help them target cancer cells. One drawback to this approach is that certain cancer cells will use a type of cloaking technology - signalling to immune cells to stop aggressive behaviour. This type of strategy can be overcome by blocking these signals with targeted antibodies, many of which are now FDA approved.
"We wanted to utilize platelets' intrinsic tendencies to accumulate at wounds and to interact with circulating tumor cells, for targeted delivery of immune checkpoint inhibitors. Interestingly, we found the antibody can be promoted to release from activated platelets in the surgical site, due to the generation of small platelet-derived microparticles upon the platelet activation. Also, aggregated platelets can help attract and boost immune cells to the surgical site"
Researchers decided to attach these antibodies to platelets in a new strategy, hoping that these cells would better deliver. Infusing antibodies directly into the blood is often inaccurate and can lead to many off-target effects, as well as autoimmune issues. Platelets on the other hand, already have a propensity to be drawn to certain cancer cells and can be activated as specific sites to unleash their antibody load. This could allow better targeting of microtumour sites across the body.
In this study researchers attached atezolizumab, an anti-PD-L1 inhibitor antibody, to the platelet cells. The results were promising, and improved survival in mice given the engineered platelets. Both cancer spread and recurrence were significantly reduced.
"It's going to be a broader technology to treat a variety of tumors. That's why we applied different cancer types—not just for solid tumors, but for cancers like leukemia. Leukemia is a liquid, circulating tumor, while breast tumors and melanoma are solid tumors, so this is going to be a very broad technology. We need new approaches to address cancer metastasis and circulating tumors after surgery, and we think we're on the right track using platelets laced with antibodies to kill various types of cancers"
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