A nanotechnology platform can make solid tumor cells more susceptible to immunotherapy

A nanotechnology platform can make solid tumor cells more susceptible to immunotherapy

A team of researchers at the University of Texas MD Anderson Cancer Center has developed a nanotechnology platform that can change the way the immune system sees solid tumor cells, making them more receptive to immunotherapy. The preclinical results suggest that this adaptable immunoconversion approach has the potential for broad application across many types of cancer.

The study, published today in Nature Nanotechnology, describes the use of this platform to artificially attach an activating molecule to the surface of tumor cells, triggering an immune response in both in vivo and in vitro models. Wen Jiang, MD, Ph.D., assistant professor of radiation oncology, and Betty Kim, MD, Ph.D., professor of neurosurgery, co-led the study.

With this new platform, we now have a strategy to convert a solid tumor, at least immunologically, into a hematological tumor, which often has a much higher response rate to immunotherapy treatments. If we are able to implement and validate this approach in the clinic, we may be able to get closer to the maximum level of activity of immunotherapeutics in cancers that have traditionally not responded well.”

Wen Jiang, MD, Ph.D., assistant professor of radiation oncology

Immunotherapy has high response rates in blood cancers such as leukemia and lymphoma, but success has been variable in solid tumors. Scientists have been working to better understand the mechanisms that prevent a better response. One explanation is that the differential expression of immune regulatory molecules on blood cancer cells compared to solid tumor cells influences how they interact with immune cells.

The SLAMF7 receptor (Lymphocytic Activation Molecule Family Member 7) is crucial for activating the body's immune cells against cancer cells and acts as an "eat me" signal. However, it is found almost exclusively on the surface of blood cancer cells and not in solid tumor cells, making it an attractive target for the researchers' immunoconversion approach.

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To promote the expression of SLAMF7 on solid tumor cells, the researchers developed their bispecific tumor-transforming nanoconjugates (BiTN) platform. These nanosystems are designed so that one molecule binds to the surface of targeted tumor cells and a second molecule activates an immune response.

In this study, researchers used BiTN with SLAMF7 and a HER2-recognizing antibody to target HER2-positive breast cancer cells. In laboratory models, the nanoconjugate SLAMF7 successfully attached to the breast cancer cells, leading to phagocytosis or uptake by immune cells. The approach also sensitized the breast cancer cells to treatment with an anti-CD47 antibody, which blocks the “don’t eat me” signal from tumor cells to further enhance responses in solid tumors.

According to the authors, one of the most exciting things about this platform is the wide range of possible applications. The approach would not be specific to any one cancer type or regulatory molecule, but has the potential to be a universal strategy across several different solid tumor types. As a proof of concept, the authors also developed BiTN with folic acid instead of the anti-HER2 antibody to target triple-negative breast cancer with similar results.

“Because these are engineered constructs, this can be used as a plug-and-play approach to integrate different tumor-targeting agents or immune molecules onto the surface of the nanoparticle,” Kim said. “For patients with solid tumors that have not responded to immunotherapy, we see this as an additional benefit to address the part of the tumor that has not responded.”

The study was supported in part by the Career Catalyst Research Grant from the Susan G. Komen Foundation, the National Cancer Institute/National Institutes of Health (1K08 CA241070, P30 CA016672), and the U.S. Department of Defense.

Source:

University of Texas MD Anderson Cancer Center

Reference:

Lu, Y., et al. (2022) Immunological transformation of solid tumors using a bispecific nanobioconjugate for cancer immunotherapy. Nature nanotechnology. doi.org/10.1038/s41565-022-01245-7.

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