Red Blood Cell-Encapsulated L-Asparaginase: Potential Therapy of Patients with Asparagine Synthetase Deficient Acute Myeloid Leukemia

被引：41

作者：

Agrawal, Vaidehi ^{[1
]}

Woo, Jung Hee ^{[1
]}

Borthakur, Gautham ^{[2
]}

Kantarjian, Hagop ^{[2
]}

Frankel, Arthur E. ^{[1
]}

机构：

[1] Scott & White Canc Res Inst, Temple, TX 76502 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA

来源：

PROTEIN AND PEPTIDE LETTERS | 2013年 / 20卷 / 04期

关键词：

Red blood cell encapsulation; L-asparaginase and AML; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRYSANTHEMI L-ASPARAGINASE; CONJUGATED L-ASPARAGINASE; EPSTEIN-BARR-VIRUS; IN-VITRO; PEG-ASPARAGINASE; STRUCTURAL BASIS; GENE-EXPRESSION; GROUP-B; CANCER;

D O I：

10.2174/092986613805290426

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：392 / 402

页数：11

共 88 条

[1] Weekly polyethylene glycol conjugated L-asparaginase compared with biweekly dosing produces superior induction remission rates in childhood relapsed acute lymphoblastic leukemia: a pediatric oncology group study [J].