Targeted lymphodepletion with a CD45-directed antibody radioconjugate as a novel conditioning regimen prior to adoptive cell therapy
| Autor: | Ravendra Garg, Eileen M. Geoghegan, Wojciech Dawicki, Mark S. Berger, Dale L. Ludwig, Kevin J. H. Allen, Ekaterina Dadachova |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment T cell Spleen 177Lutetium anti-CD45 targeted lymphodepletion Cell therapy 03 medical and health sciences 0302 clinical medicine Immune system medicine biology business.industry adoptive cell therapy Chimeric antigen receptor 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Radioimmunotherapy radioimmunotherapy biology.protein Cancer research Antibody business CD8 Research Paper 131Iodine |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.27731 |
| Popis: | Chimeric antigen receptor (CAR) T cell therapies, and adoptive cell therapy (ACT) in general, represent one of the most promising anti-cancer strategies. Conditioning has been shown to improve the immune homeostatic environment to enable successful ACT or CAR-T engraftment and expansion in vivo following infusion, and represents potential point of intervention to decrease serious toxicities following CAR-T treatment. In contrast to relatively non-specific chemotherapy-derived lymphodepletion, targeted lymphodepletion with radioimmunotherapy (RIT) directed to CD45 may be a safer and more effective alternative to target and deplete immune cells. Here we describe the results of preclinical studies with an anti-mouse CD45 antibody 30F11, labeled with two different beta-emitters 131Iodine (131I) and 177Lutetium (177Lu), to investigate the effect of anti-CD45 RIT lymphodepletion on immune cell types and on tumor control in a model of adoptive cell therapy. Treatment of mice with 3.7 MBq 131I-30F11 or 1.48 MBq 177Lu-30F11 safely depleted immune cells such as spleen CD4+ and CD8+ T Cells, B and NK cells as well as Tregs in OT I tumor model while sparing RBC and platelets and enabled E. G7 tumor control. Our results support the application of CD45-targeted RIT lymphodepletion with a non-myeloablative dose of 131I-30F11 or 177Lu-30F11 antibody prior to adoptive cell therapy. |
| Databáze: | OpenAIRE |
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