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IL-21 antibodies

總結: A novel and highly differentiated immunomodulatory therapeutic based on Interleukin-21 (IL-21) activation. Our monoclonal antibody binds to and enhances IL-21, safely activating the immune system to treat cancer and chronic viral infections.

技術優勢: - ‘Best in Class’ IL-21 agonist mAb
- Benefits over rIL-21: efficacy, safety profile, dosing regimen, duration of response
- Clinically validated mechanism of action
- Potential combination with checkpoint inhibitors and other immunotherapies

詳細技術說明: Humanised monoclonal antibody 2P2 that is an agonist of hIL-2. Binds with high affinity to IL-21 to enhance agonistic effect. Shown to stimulate B cell proliferation and CD8+ T cell cytotoxicity in vitro. Activity of endogenous IL-21 in increased ~20-fold and significantly prolongs its half-life 1/2 in vivo by ~50-fold. The crystal structure the mAb and further modelling of the IL-21 binding suggest a favourable conformational position that improves IL-21 half-life.
Studies using human IL-21/IL-21R knock-in mice reveal that 2P2 enhances the cytotoxicity of CD8+ T cells (increases the CD8/Treg and CD8/CD4 ratios in TILs and lymph nodes, increases CD8 activation, infiltration in tumour and CD8 proliferation and reduces tumour burden compared to IL-21). Current experiments show that 2P2 alone can act on endogenous IL-21 to produce the same effects. In addition, 2P2 alone reduces T cell exhaustion and viral load in an LCMV model of chronic viral infection. Taken together, these data support the notion that 2P2 activates endogenous IL-21 to mount an effective immune response.
Our 2P2 agonist mAb opportunity provides an improved IL-21 agonist approach acting on endogenous IL-21 (safety), having longer duration of action, a more convenient dosing schedule and in alignment with co-therapeutics that can act synergistically (i.e. checkpoint inhibitors).

其他: Monash seeks a partnership to progress 2P2 development, by testing efficacy in a range of experimental models (single agent and in combination with checkpoint inhibitors) and conducting formal preclinical and CMC studies. Monash researchers have significant experience in the development of therapeutic antibodies and have hIL-21 and hIL-21R knock-in mice models.

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