Radiopharmaceutical application of TRK-950, an anti-CAPRIN-1 therapeutic antibody
Abstract Purpose Tumor imaging or therapy using cancer specific carriers combined with a radioisotope has huge potential. In radiopharmaceutical development, it is important to ensure target specificity and minimal binding to normal tissues for both tumor detection and treatment. In previous studies...
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| Format: | Article |
| Language: | English |
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Springer
2025-06-01
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| Series: | Journal of Cancer Research and Clinical Oncology |
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| Online Access: | https://doi.org/10.1007/s00432-025-06236-4 |
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| author | Yuki Majima David Kryza Mitsuaki Sanada Jacqueline Sidi-Boumedine Patrick Mehlen Benjamin Gibert Jean-Yves Blay Fumiyoshi Okano |
| author_facet | Yuki Majima David Kryza Mitsuaki Sanada Jacqueline Sidi-Boumedine Patrick Mehlen Benjamin Gibert Jean-Yves Blay Fumiyoshi Okano |
| author_sort | Yuki Majima |
| collection | DOAJ |
| description | Abstract Purpose Tumor imaging or therapy using cancer specific carriers combined with a radioisotope has huge potential. In radiopharmaceutical development, it is important to ensure target specificity and minimal binding to normal tissues for both tumor detection and treatment. In previous studies, we identified CAPRIN-1 as a cancer-specific antigen, which is widely expressed on the cell surface membrane in many types of solid cancers, and created TRK-950, a humanized monoclonal antibody raised against CAPRIN-1, followed by conducting clinical development. In this proof-of-concept study, we prepared radiolabeled form of TRK-950 and investigated their potential as tumor imaging or therapeutic agents. Methods An [111In]In-DOTA-TRK-950 was prepared and administered to tumor-bearing mice, and its tumor accumulation and pharmacokinetics were evaluated with SPECT/CT imaging. Next, the anti-tumor effect of a [177Lu]Lu-DOTA-TRK-950 was evaluated. Additionally, radiolabeled TRK-950-F(ab’)2, an antibody fragment of TRK-950, was similarly evaluated for their potential. Results At 72 h after administration of [111In]In-DOTA-TRK-950, tumor accumulation was high at 24.8% IA/g for 4T1 and 18.9% IA/g for HT-29, both of which are CAPRIN-1-high cancer cells, while tumor accumulation remained low at 7.5% IA/g for MNNG/HOS, which are CAPRIN-1-low cancer cells. Regarding therapeutic evaluations, strong anti-tumor effects and prolonged survival were observed after administration of [177Lu]Lu-DOTA-TRK-950 to 4T1 and HT-29 tumor-bearing mice. Furthermore, these results were also observed in the 4T1 tumor-bearing model with radiolabeled TRK-950-F(ab’)2, which has shorter pharmacokinetics. Conclusion This study demonstrates that radiopharmaceuticals targeting CAPRIN-1, including radiolabeled TRK-950 and TRK-950-F(ab’)2, have high potential as radiopharmaceuticals. |
| format | Article |
| id | doaj-art-e890c25183ed44a1ae10d4b96243e203 |
| institution | Kabale University |
| issn | 1432-1335 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Springer |
| record_format | Article |
| series | Journal of Cancer Research and Clinical Oncology |
| spelling | doaj-art-e890c25183ed44a1ae10d4b96243e2032025-08-20T04:01:46ZengSpringerJournal of Cancer Research and Clinical Oncology1432-13352025-06-01151611110.1007/s00432-025-06236-4Radiopharmaceutical application of TRK-950, an anti-CAPRIN-1 therapeutic antibodyYuki Majima0David Kryza1Mitsuaki Sanada2Jacqueline Sidi-Boumedine3Patrick Mehlen4Benjamin Gibert5Jean-Yves Blay6Fumiyoshi Okano7Toray Industries, Inc. New Frontiers Research LaboratoriesLumen, Centre Léon BérardToray Industries, Inc. New Frontiers Research LaboratoriesImthernat Plateform, LAGEPP UMR5007Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS5286, Université Lyon 1Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS5286, Université Lyon 1Centre Léon Bérard, University Claude Bernard Lyon, UnicancerToray Industries, Inc. New Frontiers Research LaboratoriesAbstract Purpose Tumor imaging or therapy using cancer specific carriers combined with a radioisotope has huge potential. In radiopharmaceutical development, it is important to ensure target specificity and minimal binding to normal tissues for both tumor detection and treatment. In previous studies, we identified CAPRIN-1 as a cancer-specific antigen, which is widely expressed on the cell surface membrane in many types of solid cancers, and created TRK-950, a humanized monoclonal antibody raised against CAPRIN-1, followed by conducting clinical development. In this proof-of-concept study, we prepared radiolabeled form of TRK-950 and investigated their potential as tumor imaging or therapeutic agents. Methods An [111In]In-DOTA-TRK-950 was prepared and administered to tumor-bearing mice, and its tumor accumulation and pharmacokinetics were evaluated with SPECT/CT imaging. Next, the anti-tumor effect of a [177Lu]Lu-DOTA-TRK-950 was evaluated. Additionally, radiolabeled TRK-950-F(ab’)2, an antibody fragment of TRK-950, was similarly evaluated for their potential. Results At 72 h after administration of [111In]In-DOTA-TRK-950, tumor accumulation was high at 24.8% IA/g for 4T1 and 18.9% IA/g for HT-29, both of which are CAPRIN-1-high cancer cells, while tumor accumulation remained low at 7.5% IA/g for MNNG/HOS, which are CAPRIN-1-low cancer cells. Regarding therapeutic evaluations, strong anti-tumor effects and prolonged survival were observed after administration of [177Lu]Lu-DOTA-TRK-950 to 4T1 and HT-29 tumor-bearing mice. Furthermore, these results were also observed in the 4T1 tumor-bearing model with radiolabeled TRK-950-F(ab’)2, which has shorter pharmacokinetics. Conclusion This study demonstrates that radiopharmaceuticals targeting CAPRIN-1, including radiolabeled TRK-950 and TRK-950-F(ab’)2, have high potential as radiopharmaceuticals.https://doi.org/10.1007/s00432-025-06236-4TRK-950CAPRIN-1CancerTumor ImagingRadioimmunotherapy |
| spellingShingle | Yuki Majima David Kryza Mitsuaki Sanada Jacqueline Sidi-Boumedine Patrick Mehlen Benjamin Gibert Jean-Yves Blay Fumiyoshi Okano Radiopharmaceutical application of TRK-950, an anti-CAPRIN-1 therapeutic antibody Journal of Cancer Research and Clinical Oncology TRK-950 CAPRIN-1 Cancer Tumor Imaging Radioimmunotherapy |
| title | Radiopharmaceutical application of TRK-950, an anti-CAPRIN-1 therapeutic antibody |
| title_full | Radiopharmaceutical application of TRK-950, an anti-CAPRIN-1 therapeutic antibody |
| title_fullStr | Radiopharmaceutical application of TRK-950, an anti-CAPRIN-1 therapeutic antibody |
| title_full_unstemmed | Radiopharmaceutical application of TRK-950, an anti-CAPRIN-1 therapeutic antibody |
| title_short | Radiopharmaceutical application of TRK-950, an anti-CAPRIN-1 therapeutic antibody |
| title_sort | radiopharmaceutical application of trk 950 an anti caprin 1 therapeutic antibody |
| topic | TRK-950 CAPRIN-1 Cancer Tumor Imaging Radioimmunotherapy |
| url | https://doi.org/10.1007/s00432-025-06236-4 |
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