CD40 Agonists

CD40 Agonists – Target Pipeline List 04/2019

Target: CD40, TNFSFR5; tumor necrosis factor super family receptor 5

This Target Pipeline List provides an overview of CD40 agonistic biologics (antibodies, proteins, viral vectors) in development for treatment of solid tumors as monotherapy or in combination therapy.

The transmembrane protein receptor CD40 is a member of the tumor necrosis factor (TNF) receptor super family and is involved in co-stimulation of immune cells. CD40 is expressed by antigen-presenting cells (APCs) including dendritic cells (DCs), B-cells, macrophages, and monocytes. It has the ability to “wake” DCs to prime effective cytotoxic T-cell responses. Binding of an anti-CD40 antibody to CD40 on antigen presenting cells (i.e., dendritic cells, monocytes and B-cells) is believed to initiate a multi-faceted immune response that enables multiple components of the immune system (e.g., T cells, macrophages) to work in concert against cancer.

CD40 is an important target for immunotherapy, as it plays a critical role in the activation of innate and adaptive immune responses. Effective anti-CD40 antibodies provide an ideal therapy alternative in combination with other immuno-oncology (IO) antibodies. When delivered systemically, CD40 agonists have produced adverse events that may limit their use.

A number of novel CD40 targeting biologics are in preclinical and clinical development using constructs (multimeric, bispecific, targeted delivery) to overcome systemic safety issues by limiting activation to the tumor microenvironment.

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