Medical Microbiology and Bioprocess Technology Laboratory, Department of Microbiology, Maharshi Dayanand University, Rohtak, Haryana, India.
Molecular Biology and Genetic Engineering Laboratory, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India.
Appl Microbiol Biotechnol. 2020 Apr;104(7):2857-2869. doi: 10.1007/s00253-020-10432-2. Epub 2020 Feb 10.
Amino acid deprivation therapy (AADT) is emerging as a promising strategy for the development of novel therapeutics against cancer. This biological therapy relies upon the differences in the metabolism of cancer and normal cells. The rapid growth of tumors results in decreased expression of certain enzymes leading to auxotrophy for some specific amino acids. These auxotrophic tumors are targeted by amino acid-depleting enzymes. The depletion of amino acid selectively inhibits tumor growth as the normal cells can synthesize amino acids by their usual machinery. The enzymes used in AADT are mostly obtained from microbes for their easy availability. Microbial L-asparaginase is already approved by FDA for the treatment of acute lymphoblastic leukemia. Arginine deiminase and methionase are under clinical trials and the therapeutic potential of lysine oxidase, glutaminase and phenylalanine ammonia lyase is also being explored. The present review provides an overview of microbial amino acid depriving enzymes. Various attributes of these enzymes like structure, mode of action, production, formulations, and targeted cancers are discussed. The challenges faced and the combat strategies to establish AADT in standard cancer armamentarium are also reviewed.Key Points • Amino acid deprivation therapy is a potential therapy for auxotrophic tumors. • Microbial enzymes are used due to their ease of manipulation and high productivity. • Enzyme properties are improved by PEGylation, encapsulation, and genetic engineering. • AADT can be employed as combinational therapy for better containment of cancer.
氨基酸剥夺疗法（Amino acid deprivation therapy，AADT）作为一种针对癌症的新型治疗策略正在兴起。这种生物疗法依赖于癌症和正常细胞代谢的差异。肿瘤的快速生长导致某些酶的表达降低，导致某些特定氨基酸的营养缺陷。这些营养缺陷型肿瘤是氨基酸耗竭酶的靶向目标。由于正常细胞可以通过其常用机制合成氨基酸，因此氨基酸的消耗选择性地抑制肿瘤生长。AADT 中使用的酶主要从微生物中获得，因为它们容易获得。微生物 L-天冬酰胺酶已被 FDA 批准用于治疗急性淋巴细胞白血病。精氨酸脱氨酶和蛋氨酸酶正在进行临床试验，赖氨酸氧化酶、谷氨酰胺酶和苯丙氨酸氨裂解酶的治疗潜力也在探索中。本综述概述了微生物氨基酸剥夺酶。讨论了这些酶的各种特性，如结构、作用模式、生产、配方和靶向癌症。还回顾了在标准癌症武器库中建立 AADT 所面临的挑战和应对策略。
氨基酸剥夺疗法是营养缺陷型肿瘤的一种潜在治疗方法。
由于易于操作和高生产力，微生物酶被用于 AADT。
通过聚乙二醇化、封装和遗传工程来改善酶的特性。
AADT 可以作为联合治疗方法，更好地控制癌症。
