Overcoming resistance with designer immunotoxins.
Normal human serum contains apolipoprotein L-I (apoL-I), which lyses African trypanaosomes. Resistant forms, such as Trypanosoma brucei rhodesiense express apoL-I-neutralising serum resistance-associated protein, which enables this parasite to infect humans and cause human African trypanosomiasis. This paper describes the construction of a mutant apoL-I conjugated to a nanobody that targets the variant surface glycoprotein of trypanosomes. Treatment with this engineered immunotoxin has resulted in both alleviating and curative effects on chronic and acute infections of mice with normal human serum-resistant and -sensitive trypanosomes.
Braddock
Martin
M
Discovery Bioscience, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, Leicestershire, LE11 5RH, UK. martin.braddock@astrazeneca.com