ライス大学とベイラー医科大学の研究により、侵襲性の高い肺がんに対する治療法の可能性に注目。 Rice, Baylor study highlights potential treatment for aggressive lung cancer
2022-08-22 ライス大学
研究者らは、ピンの頭ほどの大きさの薬物生成ビーズを腫瘍のそばに投与し、白血球を活性化してがんと闘う天然化合物であるインターロイキン2(IL-2)を継続的かつ大量に生成することができた。
サイトカイン工場は、アルギン酸ビーズに、FDAががん治療用に承認した2種類のサイトカインのうちの1つである天然のIL-2を産生するように遺伝子操作された数万個の細胞を充填したものである。この細胞工場は幅がわずか1.5ミリメートルで、低侵襲手術で移植することができ、高用量のIL-2を腫瘍に直接投与することができる。中皮腫の研究では、ビーズは腫瘍の脇と、肺を覆い胸の内壁を覆う胸膜と呼ばれる薄い組織の層の内側に置かれた。
<関連情報>
- https://news.rice.edu/news/2022/drug-factory-implants-eliminate-mesothelioma-tumors-mice
- https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-22-1493/707851/Activation-of-adaptive-and-innate-immune-cells-via
インターロイキン-2サイトカインファクトリーの局在化による適応・自然免疫細胞の活性化で中皮腫腫瘍を撲滅 Activation of adaptive and innate immune cells via localized Interleukin-2 cytokine factories eradicates mesothelioma tumors
Amanda M. Nash;Samira Aghlara-Fotovat;Bertha Castillio;Andrea Hernandez;Aarthi Pugazenthi;Hyun-Sung Lee;Hee-Jin Jang;Annie Nguyen;Alexander Lu;Bryan M. Burt;Ravi K. Ghanta;Omid Veiseh
Clinical Cancer Research Published;August 22 2022
DOI:https://doi.org/10.1158/1078-0432.CCR-22-1493
Abstract
Purpose: Interleukin-2 (IL-2) immunotherapy has the potential to elicit immune-mediated tumor lysis via activation of effector immune cells, but clinical utility is limited due to pharmacokinetic challenges as well as vascular leak syndrome and other life-threatening toxicities experienced by patients. We developed a safe and clinically translatable localized IL-2 delivery system to boost the potency of therapy while minimizing systemic cytokine exposure. Experimental Design: We evaluated the therapeutic efficacy of IL-2 cytokine factories in a mouse model of malignant mesothelioma. Changes in immune populations were analyzed using time-of-flight mass cytometry (CyTOF), and the safety and translatability of the platform were evaluated using complete blood counts and serum chemistry analysis. Results: IL-2 cytokine factories enabled 150x higher IL-2 concentrations in the local compartment with limited leakage into the systemic circulation. AB1 tumor burden was reduced by 80% after one week of monotherapy treatment, and 7/7 of animals exhibited tumor eradication without recurrence when IL-2 cytokine factories were combined with aPD1. Further, CyTOF analysis showed an increase in CD69+CD44+ and CCD69-CD44+CD62L+ T cells, reduction of CD86-PD-L1- M2-like macrophages, and a corresponding increase in CD86+PD-L1+ M1-like macrophages and MHC II+ dendritic cells after treatment. Finally, blood chemistry ranges in rodents demonstrated the safety of cytokine factory treatment and reinforced its potential for clinical use. Conclusion: IL-2 cytokine factories led to the eradication of aggressive mouse MM tumors, protection from tumor recurrence, and increased the therapeutic efficacy of anti-PD1 checkpoint therapy. This study provides support for the clinical evaluation of this IL-2-based delivery system.
