Agrawal Vaidehi, Woo Jung Hee, Borthakur Gautham, Kantarjian Hagop, Frankel Arthur E
Scott & White Cancer Research Institute, Temple, TX 76502, USA.
Protein Pept Lett. 2013 Apr;20(4):392-402.
Red blood cell (RBC) encapsulated L-asparaginase is a novel therapeutic for the treatment of asparagine auxotrophic malignancies. The enzyme-loaded red blood cells function as bioreactors to deplete bloodstream substrate. This delivery system provides improved pharmacodynamics with protection from circulating proteolytic enzymes and avoidance of early liver or renal clearance. The "drug" is manufactured with ABO and Rh compatible donor blood when a prescription is received. Because of the industrial scale manufacturing, the "drug" is transfused the day of receipt at the clinical site. Preliminary clinical studies show utility in childhood and adult acute lymphoblastic leukemia. Based on previous studies of applications in different diseases and assessment of different biomarkers, we propose this agent offers a safe and potentially effective treatment for a subset of chemotherapy refractory acute myeloid leukemia patients. The history, chemistry, biology, pharmacology, and relevant clinical experiences with L-asparaginase as well as the properties and proposed protocols with the red cell-encapsulated enzyme are reviewed.
红细胞包封的L-天冬酰胺酶是一种用于治疗天冬酰胺营养缺陷型恶性肿瘤的新型疗法。载有该酶的红细胞起到生物反应器的作用，以耗尽血液中的底物。这种递送系统改善了药效学，可保护其免受循环中的蛋白水解酶的影响，并避免早期肝脏或肾脏清除。当收到处方时，该“药物”由ABO和Rh血型相容的献血者血液制成。由于是工业化规模生产，该“药物”在临床场所收到当天就进行输注。初步临床研究表明其在儿童和成人急性淋巴细胞白血病中有效。基于先前在不同疾病中的应用研究以及对不同生物标志物的评估，我们认为该药物为一部分化疗难治性急性髓细胞白血病患者提供了一种安全且可能有效的治疗方法。本文综述了L-天冬酰胺酶的历史、化学、生物学、药理学及相关临床经验，以及红细胞包封酶的特性和拟定方案。
