Research Projects

Asparaginase (ASNase) is a first-line therapy for Acute lymphoblastic leukemia (ALL), affecting the blood, bone marrow, and lymphoid system. It has been shown to improve the overall survival of childhood ALL, but it has several adverse side effects, including immunogenicity, hypersensitivity, anaphylaxis, short half-life, and glutaminase activity. To address these issues, a protein engineering approach was used to create an ASNase mutant (M-ASPAR) with amino acid replacement at subunit interfaces and B-cell epitopes. This non-naturally occurring variant reduced immunogenicity in vivo in mice and ALL patients, improved stability, and reduced elimination rate. It also showed negligible glutaminase side activity and increased cytotoxicity against blast cells, leaving healthy non-leukemic cells unaffected. The M-ASPAR variant also showed improved pharmacokinetic properties than the wild type EcA. This invention could be used as an anti-leukemic agent for primary and relapsed ALL treatment in the future. The researchers have filed two patents, one granted on April 29, 2021, and the other on September 27, 2021, supported by DST-SERB Grants.