التفاصيل البيبلوغرافية
| العنوان: |
Low-dose targeted radionuclide therapy synergizes with CAR T cells and enhances tumor response. |
| المؤلفون: |
Yanping Yang, Vedvyas, Yogindra, Alcaina, Yago, Son, Ju Y., Min, Irene M., Jin, Moonsoo M. |
| المصدر: |
Frontiers in Immunology; 2024, p1-11, 11p |
| مصطلحات موضوعية: |
CHIMERIC antigen receptors, POSITRON emission tomography, T cells, RADIOISOTOPES, SOMATOSTATIN receptors |
| مستخلص: |
Ionizing radiation has garnered considerable attention as a combination partner for immunotherapy due to its potential immunostimulatory effects. In contrast to the more commonly used external beam radiation, we explored the feasibility of combining chimeric antigen receptor (CAR) T cell therapy with targeted radionuclide therapy (TRT), which is achieved by delivering β-emitting 177Lu- DOTATATE to tumor via tumor-infiltrating CAR T cells that express somatostatin receptor 2 (SSTR2). We hypothesized that the delivery of radiation to tumors could synergize with CAR T therapy, resulting in enhanced antitumor immunity and tumor response. To determine the optimal dosage and timing of 177Lu- DOTATATE treatment, we measured CAR T cell infiltration and expansion in tumors longitudinally through positron emission tomography (PET) using a SSTR2-specific positron-emitting radiotracer, 18F-NOTA-Octreotide. In animals receiving CAR T cells and a low-dose (2.5 Gy) of TRT following the administration of 177Lu-DOTATATE, we observed a rapid regression of large subcutaneous tumors, which coincided with a dramatic increase in serum proinflammatory cytokines. Tumor burden was also reduced when a higher radiation dose (6 Gy) was delivered to the tumor. However, this higher dose led to cell death in both the tumor and CAR T cells. Our study suggests that there may exist an optimum range of TRT dosage that can enhance T cell activity and sensitize tumor cells to T cell killing, which may result in more durable tumor control compared to a higher radiation dose. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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