A bispecific antibody to synergise checkpoint blockers in oncology

Project: Research

Project Details

Project Description

This proposal seeks to advance a discovery made in our laboratory by performing proof-of-concept studies with bispecific therapeutic antibodies targeting the chemokine receptors CXCR1 and CXCR2 present on the surface of myeloid-derived suppressor cells (MDSC). Such drugs represent novel, effective yet safe treatments for solid tumors when use in combination with immune checkpoint blockers (ICBs). MDSC is the most important cell of the tumor microenvironnemt (TME) and protect the tumor from the patient’s immune system and immunotherapy. The future of cancer treatment is combination therapy with drugs that improve effector functions (ICBs) and synergize with therapies that target the suppressive role of the TME. We believe that the best combination treatment will be ICB therapy combined with a therapy that block the migration of MDSC to the TME. We have recently developed an approach with the potential to address this clinical need by targeting simultaneously the drivers of MDSCs migration to the TME, CXCR1 and CXCR2 with a unique bispecific antibody.
In initial proof-of-principles studies, we have developed an innovative drug which has been the holy grail of chemokine research- an effective and safe inhibitor of all CXCR1 and CXCR2 chemokine ligands. We selected antibodies to human CXCR1 and CXCR2 that shared identical Ig light chains, making the bi-specific engineering highly viable. We are supported by a leading company with a history of creating and commercialising human therapeutic antibodies and with a major interest in therapies for cancer (Corvus Pharma).
The current application seeks to perform the next stage proof-of-concept studies that will lead directly to clinical trial of the agent. Specifically we will:
1) Humanize and characterize in vitro a novel bispecific antibody with a common Ig light chain
2) Evaluate the potency of the bispecific antibody in combination with checkpoint inhibitors using double human knock-in CXCR1/2 mice
StatusActive
Effective start/end date1/01/2131/12/23

Keywords

  • antibody engineering
  • antibody cancer therapy
  • tumour immunotherapy
  • chemokine receptor
  • immune evasion