ReTenTion · Next Generation Immune Checkpoint Inhibitor for Cancer Therapy

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Project objective

Immune checkpoint inhibitors (ICIs) for cancer therapy have revolutionized the treatment of several cancers. These ICIs are made from monoclonal antibodies that antagonize inhibitory signals via cytotoxic T-lymphocyte- associated antigen-4 (CTLA-4) and programmed cell death protein-1 (PD-1) that block the tumoricidal activity of T cells. Although these ICIs have improved the overall survival of cancer patients such as cutaneous melanoma patients, only one third of patients has remained progression-free 5 years after initiating ICI therapy. This low efficacy is largely due to (1) the presence of immune suppressive regulatory T cells (Treg) within tumor microenvironment (TME) (2) the lack of efficacy of tumor penetration and retention. To improve the current ICI, this project RenTenTion aims to develop a next generation ICIs with smaller molecule so called single domain antibody (sdAb), give rise to enhanced tumor penetration. Targeting against a new immune checkpoint molecule 41-BB that highly expressed by intratumoral Treg, this next generation sdAb based ICI will inhibit tumor promoting immune cells Treg, while stimulate tumor rejecting immune cells such as effector T cells in tumors. Additionally, this project will couple the sdAb with collagen binding domain receptor so called leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) that bind to collagen in the tumor, therefore sustain tumor retention. This project “ReTenTion” will fill a gap for a strong need for new ICI molecules capable of addressing immunosuppressive in TME, yet smaller than conventional ICIs, boosting passive delivery.

Original text from CORDIS.

Participants

• VRIJE UNIVERSITEIT BRUSSEL · Bruxelles / BrusselCoordinatorBelgium
• ETHERNA IMMUNOTHERAPIES · NielBelgium

Links

• View on CORDIS
• DOI: 10.3030/101205497