by Free University of Brussels

The ^99mTechnetium-labeled anti-CD163 immunotracer shows specific in vivo binding to CD163⁺ cells. (A and B) Representative μSPECT/CT images (3D MIP) of CD163 knock-out (−/−) and wild-type (WT) mice intravenously injected with the (A) ^99mTechnetium-labeled irrelevant nanobody (^99mTc-Irr Nb) and (B) ^99mTechnetium-labeled anti-CD163 immunotracer (^99mTc-anti-CD163 Nb) (N = 3). Cervical LN, SG, liver, K, Int, Bl, and BM are highlighted in WT mice. (C–F) Ex vivo uptake values are shown of the liver, spleen, cervical LN, and BM from CD163^−/− and WT mice. (G) An overview of ex vivo uptake values of all isolated organs from WT and CD163^−/− mice. Data of three mice are shown and plotted as mean ± SD of the percentage of injected activity per gram of organ or tissue (%IA/g). Statistical analysis was performed using an unpaired two-tailed t test. ns, P > 0.05; *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001. Credit: Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2409668121

Immunotherapy is a type of cancer treatment that stimulates a patient's immune system to attack tumors. While promising, its effectiveness varies among patients. The new VUB technology helps identify in advance which patients are likely to benefit from this treatment. The findings are published in the journal Proceedings of the National Academy of Sciences.

The study introduces an innovative tracer targeting CD163, a molecular receptor on tumor-associated macrophages—immune cells that support tumor growth and protection. The tracer is based on nanobodies, small and versatile antibodies derived from camelids like llamas, which can penetrate deep into tissues.

Using scans, researchers can measure the quantity of these macrophages within a tumor. A higher number of macrophages suggests the tumor is more resistant to treatment, making immunotherapy less effective. This allows doctors to predict which patients will respond best to the therapy.

"You can compare a tumor to a secret gang, not just made up of cancer cells but also other cells working together. Some of these cells, the tumor-associated macrophages, pretend to be on the good side but actually help the tumor grow and shield it from treatments.

"Our new nanobody tracer acts like a detective, locating and highlighting these macrophages using specialized scans. This helps us understand their behavior and how to target them. For patients, this means we can better predict which treatment will work best, avoiding unnecessary treatments and side effects," explains Professor Timo De Groof from the Molecular Imaging and Therapy research group (MITH) at VUB.

Benefits of the nanobody tracer:

• Specific and safe: The tracer exclusively binds to CD163+ macrophages without disrupting the immune system.

• Quick therapy assessment: Mapping CD163+ macrophages helps determine whether immunotherapy is effective.

• Broad applications: The technology may also be used for inflammatory conditions like atherosclerosis and arthritis, where CD163+ macrophages play a critical role.

Professor Nick Devoogdt, head of the MITH research group, highlights that this discovery marks an important step toward personalized medicine. "This technology enables us to tailor therapies to individual patients, making treatments more effective."

Professor Jo Van Ginderachter of the VIB Center for Inflammation Research and the Brussels Center for Immunology adds, "This opens new doors not only in oncology but also in other diseases involving the immune system."

More information: Yoline Lauwers et al, Imaging of tumor-associated macrophage dynamics during immunotherapy using a CD163-specific nanobody-based immunotracer, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2409668121

Journal information: Proceedings of the National Academy of Sciences 

Provided by Free University of Brussels