دورية أكاديمية
436 Immunotherapy Sensitization via Tumor Acidosis Mitigation by Esomeprazole Monitored with MRI
| العنوان: | 436 Immunotherapy Sensitization via Tumor Acidosis Mitigation by Esomeprazole Monitored with MRI |
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| المؤلفون: | Murley, Grace Abigail, Pudakalakatti, Shivanand, Padron, William, Wang, Muxin, Armijo, Ryan, Delacerda, Jorge, Dominic, Abishai, Chin, Renee, Schuler, William, Rai, Kunal, Pagel, Marty, Bhattacharya, Pratip |
| المصدر: | Journal of Clinical and Translational Science ; volume 8, issue s1, page 130-130 ; ISSN 2059-8661 |
| بيانات النشر: | Cambridge University Press (CUP) |
| سنة النشر: | 2024 |
| الوصف: | OBJECTIVES/GOALS: Acidity and the lactate-to-pyruvate ratio correlate with immunotherapy resistance. AcidoCEST MRI and hyperpolarized magnetic resonance spectroscopy (HP-MRS) measure extracellular pH and lactate-to-pyruvate ratio. We will establish a baseline for these biomarkers then observe changes after combination esomeprazole and immunotherapy. METHODS/STUDY POPULATION: We used multiple melanoma models created via serial in vivo passage under immunotherapeutic pressure (FVAX, CTLA-4, PD-1, PD-L1). We used four of these corresponding to 25%, 50%, 75% and 100% resistance (TMT, F2, F3, and F4, respectively). HP-MRS was performed two weeks post implantation in male BL6 mice with AcidoCEST MRI 2-3 days later. Tumors were implanted in additional mice and grown for 1 week. We used esomeprazole as a possible immunotherapy sensitizer. Esomeprazole (or PBS) alone and in combination with immune checkpoint blockade (ICB; αCTLA-4, αPD-1) was then conducted every 3 days for 3 doses. ICB was administered 3h after esomeprazole. AcidoCEST MRI was performed the day after the final dose of combination therapy and 3h after esomeprazole (or PBS) alone. HP-MRS was performed 2-3 days after acidoCEST MRI. RESULTS/ANTICIPATED RESULTS: There was a statistical increase in the lactate-to-pyruvate ratio of the F4 group compared with TMT, F2, and F3 groups (p < 0.05). The TMT, F2, and F3 groups did not differ significantly. The extracellular pH (pHe) of the TMT group was statistically lower than the F2 and F4 groups (p < 0.05). The pHe did not differ significantly between the TMT and F3 groups nor the F2, F3, and F4 groups. The lactate-to-pyruvate ratio and pHe after combination treatment with esomeprazole and ICB did not differ compared to PBS+ICB control. Treatment with esomeprazole alone generated higher lactate-to-pyruvate ratio compared with PBS alone. Tumor volume curves and survival curves of mice bearing F4 tumors treated with esomeprazole combination with ICB showed no difference compared with PBS+ICB, PBS alone, and ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1017/cts.2024.376 |
| الإتاحة: | https://doi.org/10.1017/cts.2024.376Test https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S2059866124003765Test |
| حقوق: | https://creativecommons.org/licenses/by-nc-nd/4.0Test/ |
| رقم الانضمام: | edsbas.C3DE60C6 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1017/cts.2024.376 |
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