Clin Cancer Res: The activity of the trisexual T-cell activation protein HPN536 in malignant tumors that express mesothionin

Mesothelin (MSLN) is a glyphosate inositol (GPI)-connected tumor antigen that has been expressed in a variety of malignant tumors, including ovarian, pancreatic, lung and triple-negative breast cancers.
Early indications of the clinical efficacy of MSLN-targeted drugs have confirmed MSLN as a promising therapeutic intervention, but more effective treatments are needed to address the unseeded medical needs of cancers that express MSLN.
Elen and others have designed a 53 kDa three-specific T-cell activation protein-based structure, HPN536, which binds to tumor cells that express MSLN, CD3 and serum albumin on the surface of T cells.
the effectiveness, activity and half-life of HPN536 in laboratory, rodent models and non-human primates (NHPs) were evaluated through experiments.
HPN536 can effectively inhibit tumor growth experimental results confirmed that HPN536 can be combined with tumor cells expressing MSLN, and with the surface of T cells CD3, resulting in T cell activity and effective redirect target cell dissolution.
the third domain of HPN536 in combination with serum albumin can prolong the half-life of its plasma.
In crab-eating monkeys, HPN536 showed pharmacological activity and good tolerance of MSLN dependence over a dose range of 0.1-10 mg/kg;
HPN536 was given, the tissue expressing MSLN showed reversible growth and inflammation, and HPN536 showed good anti-tumor activity in the NHP model, and had good tolerance and extended half-life.
phase I clinical trial of malignant tumors expressing MSLN is currently under way (NCT03872206).