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4-1BB Multi-Functional Monoclonal Antibodies: Stimulating T cell Immunity to Treat Cancer

The Opportunity: 

Licensing opportunity around FcɣR-independent “super-agonistic” 4-IBB mABs containing a propriety hinge technology that induces CD8+ T cell activation and intratumoral Treg cell depletion.

The Technology: 

This is a licencing opportunity for IP and materials around a series of novel human and murine antibodies specific for 4-1BB antigens, covering multiple different complementarity-determining region (CDR) sequences. Also included are methods for their use in stimulation of anti-tumour T cell immunity as a monotherapy or in combination with other therapeutic moieties. These antibodies utilise a proprietary technology that enables generation of hinge-engineered FcγR independent agonistic antibodies with added therapeutic benefit over that of other anti-4-1BB antibodies in development.

4-1BB is a member of the TNFR superfamily. It is a costimulatory receptor expressed on activated immune cells, including activated T cells, and it is a highly promising target for cancer therapy. Antibodies targeting 4-1BB have been shown to enhance the proliferation and survival of antigen-stimulated T cells in vitro and promote CD8 T-cell dependent anti-tumour immunity in preclinical cancer models. It has also been shown that Treg cells infiltrating human or murine tumours express high amounts of 4-1BB.

These anti-4-1BB monoclonal antibodies have been used to preferentially deplete intra-tumoral Treg cells in vivo. The antibodies also promoted effector T cell agonism to promote tumour rejection. These distinct mechanisms were shown to be competitive and dependent on antibody isotype and FcγR availability.

Administration of anti-4-1BB IgG2a, which preferentially depletes Treg cells, followed by either agonistic anti-4-1BB IgG1 or anti-PD-1 monoclonal antibodies, augmented anti-tumour responses in multiple solid tumour models. An antibody engineered to optimize both FcγR-dependent Treg cell depleting capacity and FcγR-independent agonism delivered enhanced anti-tumour therapy.

Based on these data, these antibodies have strong potential for clinical benefit. The mechanistic insights gained into the effector mechanisms by the development team provide a robust foundation for their translation and downstream commercialisation.

Intellectual Property: 

Patent family WO 2017/077085 ( protecting antibodies generated towards 4-1BB and their therapeutic application. US and EU pending.