ArticleMolecular cancer therapeutics2022
Targeted Radionuclide Therapy with Low and High-Dose Lutetium-177-Labeled Single Domain Antibodies Induces Distinct Immune Signatures in a Mouse Melanoma Model.
Article in Molecular cancer therapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
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- Immune modulation following α and βOncoimmunology · 2025Article
- The molecular blueprint of targeted radionuclide therapy.Nature reviews. Clinical oncology · 2025Review
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- CB307: A Dual Targeting Costimulatory Humabody VH Therapeutic for Treating PSMA-Positive Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Cell Model for Testing Pharmaceuticals Targeting Human PD-L1.Sovremennye tekhnologii v meditsine · 2024Article
- Alpha Particle-Emitting Radiopharmaceuticals as Cancer Therapy: Biological Basis, Current Status, and Future Outlook for Therapeutics Discovery.Molecular imaging and biology · 2023Review
- Radiopharmaceuticals as combinatorial partners for immune checkpoint inhibitors.Trends in cancer · 2023Review
- Optimizing the Safety and Efficacy of Bio-Radiopharmaceuticals for Cancer Therapy.Pharmaceutics · 2023Article
- Cure of Disseminated Human Lymphoma with [Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2023Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targeted radionuclide therapy (TRT) using probes labeled with Lutetium-177 (177Lu) represents a new and growing type of cancer therapy. We studied immunologic changes in response to TRT with 177Lu labeled anti-human CD20 camelid single domain antibodies (sdAb) in a B16-melanoma model transfected to express human CD20, the target antigen, and ovalbumin, a surrogate tumor antigen. High-dose TRT induced melanoma cell death, calreticulin exposure, and ATP-release in vitro. Melanoma-bearing mice received fractionated low and high-dose TRT via tumor targeting anti-human CD20 sdAbs, as opposed to control sdAbs. Tumor growth was delayed with both doses. Low- and high-dose TRT increased IL10 serum levels. Low-dose TRT also decreased CCL5 serum levels. At the tumor, high-dose TRT induced a type I IFN gene signature, while low-dose TRT induced a proinflammatory gene signature. Low- and high-dose TRT increased the percentage of PD-L1pos and PD-L2pos myeloid cells in tumors with a marked increase in alternatively activated macrophages after high-dose TRT. The percentage of tumor-infiltrating T cells was not changed, yet a modest increase in ovalbumin-specific CD8pos T-cells was observed after low-dose TRT. Contradictory, low and high-dose TRT decreased CD4pos Th1 cells in addition to double negative T cells. In conclusion, these data suggest that low and high-dose TRT induce distinct immunologic changes, which might serve as an anchoring point for combination therapy.
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