Amino acid deprivation using enzymes as a targeted therapy for cancer and viral infections

Abstract

Amino acid depletion in the blood serum is currently being exploited and explored for therapies in tumors or viral infections that are auxotrophic for a certain amino acid or have a metabolic defect and cannot produce it. The success of these treatments is because normal cells remain unaltered since they are less demanding and/or can synthesize these compounds in sufficient amounts for their needs by other mechanisms. Areas covered: This review is focused on amino acid depriving enzymes and their formulations that have been successfully used in the treatment of several types of cancer and viral infections. Particular attention will be given to the enzymes L-asparaginase, L-arginase, L-arginine deiminase, and L-methionine-γ-lyase. Expert opinion: The immunogenicity and other toxic effects are perhaps the major limitations of these therapies, but they have been successfully decreased either through the expression of these enzymes from other organisms, recombination processes, pegylation of the selected enzymes or by specific mutations in the proteins. In 2006, FDA has already approved the use of L-asparaginase in the treatment of acute lymphoblastic leukemia. Other enzymes and in particular L-arginase, L-arginine deiminase, and L-methioninase have been showing promising results in vitro and in vivo studies.

Fueling influenza and the immune response: Implications for metabolic reprogramming during influenza infection and immunometabolism

“…IAV induces aerobic glycolysis in virus-producing cells and increases glutaminolysis and FA synthesis, presumably to provide carbon sources and energy to fuel virion replication while maintaining infected cell survival (Figure 1 bottom). 9,59 In the 1950s, virologists determined excess glucose and glycolysis were required for maximal IAV replication and virulence, irrespective of the host reservoir. 3,6,7 In the same decade, researchers discovered phagocytosis by polymorphonuclear leukocytes was glucose-dependent, and they attributed inhibition of phagocytosis to blocked energy metabolism.…”

Efficacy and tolerance of GELOXD/P‐GEMOXD in newly diagnosed nasal‐type extranodal NK/T‐cell lymphoma: A multicenter retrospective study

“…As such, the use of ASP can produce an anticancer effect by breaking down circulating asparagine and leaving cancer cells unable to synthesize necessary nucleic acids and proteins. 11,12 Several retrospective studies showed that gemcitabine, oxaliplatin, and l-ASP (GELOX) and gemcitabine, oxaliplatin, and pegasparaginase (P-GEMOX) regimens were effective and well tolerated in patients with ENKTCL in several previous retrospective studies. [13][14][15] However, the sample size of these retrospective studies was relatively small.…”

L‐asparaginase isolated fromStreptomyces ansochromogenespromotes Th1 profile and activatesCD8+T cells in humanPBMC: anin vitroinvestigation

“…Bioactive molecules from many micro-organisms, such as the L-asparaginase enzyme, have been isolated and investigated (Savitri and Azmi 2003;Narta et al 2007). Lasparaginase is an enzyme used as a first-line treatment of patients with ALL and paediatric AML (Samudio and Konopleva 2013) and this enzyme possesses different effects depending on which micro-organism it is extracted from (Narta et al 2007;Fernandes et al 2016). Our study evaluated a new L-asparaginase enzyme extracted from Streptomyces ansochromogenes UFPEDA 3420 actinobacteria.…”