Using nanotechnology, researchers have created a platform that can alter how the immune system perceives solid tumor cells, making them more susceptible to immunotherapy. Preclinical results suggest that this adaptive immune conversion strategy may broadly apply to various cancer types.
The work, which was just released in Nature Nanotechnology, describes the deployment of this platform to in vitro and in vivo models to artificially attach an activation molecule to the surface of tumor cells.
The study was co-led by Betty Kim, MD, PhD, professor of neurosurgery, and Wen Jiang, MD, PhD, assistant professor of radiation oncology.
At one end of the chip, they added one drop of culture media from lung cancer cells, and on the other end, the researchers added media from normal lung fibroblasts.
Nanotechnology Can Now Make Therapy More Effective vs. Cancer
In a preclinical trial, a group of researchers at The University of Texas MD Anderson Cancer Center attached immune-activating chemicals to tumors using nanoparticles to make them sensitive to immunotherapy.
"With this new platform, we now have a strategy to convert a solid tumor, at least immunologically, to resemble a hematological tumor, which often has a much higher response rate to immunotherapy treatments," Jiang said per Phys.org.
Immunotherapy has a high response rate in blood malignancies like leukemia and lymphoma. In contrast, results in solid tumors have been inconsistent. Researchers have been trying to uncover the processes that prevent a better reaction. One reason is that different immune regulatory molecules express differently in solid tumor cells against blood cancer cells, which affects how the latter interact with immune cells.
The SLAMF7 receptor, which serves as a "eat me" signal for the body's immune system, is essential for triggering defenses against cancer cells. However, since it is almost exclusively present on the surface of blood cancer cells rather than solid tumor cells, the immunological conversion strategy used by the researchers makes it a desirable target.
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How Nanotechnology Works
The researchers created their bispecific tumor-transforming nanoconjugate (BiTN) technology to encourage SLAMF7 expression on solid tumor cells. These nanosystems have two molecules-one to attach to the surface of the targeted tumor cells and the other to trigger an immune response.
To specifically target HER2-positive breast cancer cells in this work, the researchers combined BiTN with SLAMF7 and a HER2-recognizing antibody. The nanoconjugate effectively linked SLAMF7 to the breast cancer cells in laboratory models, leading to phagocytosis, or swallowing, by immune cells. SciTechDaily said the method also made breast cancer cells more responsive to therapy with an anti-CD47 antibody, which counteracts tumor cells' "don't eat me" signals to boost responses in solid tumors.
The authors claim that this platform's wide range of possible applications is one of its most fascinating features. The method has the potential to be a general approach for a variety of solid tumor types rather than being particular to one cancer type or regulatory molecule. The authors also created BiTN using folate instead of the anti-HER2-antibody to target triple-negative breast cancer with comparable outcomes as a proof of concept.
As designed constructions, they may be utilized as a plug-and-play method to attach various immune molecules or tumor-targeting medicines to the surface of nanoparticles, according to Kim. "We see this as an additional advantage to target the part of the tumor that didn't respond for patients with solid tumors that have not responded to immunotherapy."
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