Targeting CD40 with bispecifics to outsmart tumours

An interview with Dr. John Stagg, CSO of Argenx

CD40 is a cell surface protein that is expressed on antigen-presenting cells (APCs) such as dendritic cells, macrophages, and B cells. It is involved in the regulation of immune responses, and its activation can lead to the maturation of APCs and the production of cytokines such as interleukin-12 (IL-12) and interleukin-23 (IL-23). These cytokines are important for the activation of cytotoxic T cells and the generation of anti-tumor immune responses.

Bispecific antibodies are a class of antibodies that can bind to two different antigens. They can be used to redirect immune cells to target cancer cells, and have shown promise in the treatment of a variety of cancers including lymphoma, leukemia, and solid tumors.

In this interview, we speak to Dr. John Stagg, CSO of Argenx, about the company's bispecific antibody targeting CD40 and its potential for treating cancer.

What is the rationale for targeting CD40 with bispecifics?

CD40 is an attractive target for cancer immunotherapy because it is expressed on APCs, which are essential for the activation of the immune system. By targeting CD40 with bispecifics, we can redirect immune cells to cancer cells and stimulate the production of cytokines that are important for the generation of anti-tumor immune responses.

How does Argenx's bispecific antibody targeting CD40 work?

Argenx's bispecific antibody targeting CD40 is a humanized monoclonal antibody that binds to CD40 on APCs and to CD3 on T cells. This binding brings the T cells into close proximity with the APCs, which leads to the activation of the T cells and the production of cytokines such as IL-12 and IL-23. These cytokines are important for the activation of cytotoxic T cells and the generation of anti-tumor immune responses.

What are the potential benefits of using bispecifics to target CD40?

There are several potential benefits of using bispecifics to target CD40. First, bispecifics can be designed to bind to specific antigens on cancer cells, which allows for targeted delivery of immune cells to the tumor microenvironment. Second, bispecifics can activate immune cells in a more potent and sustained manner than traditional monoclonal antibodies, which can lead to improved anti-tumor efficacy.

What are the challenges of developing bispecifics targeting CD40?

There are several challenges associated with the development of bispecifics targeting CD40. One challenge is the manufacturing of these antibodies, as they are more complex to produce than traditional monoclonal antibodies. Another challenge is the potential for off-target effects, as bispecifics can bind to multiple antigens. Additionally, bispecifics can be immunogenic, which can lead to the development of anti-drug antibodies and reduced efficacy.

What are the future directions for bispecifics targeting CD40?

The future of bispecifics targeting CD40 is promising. There are several clinical trials currently underway to evaluate the safety and efficacy of these antibodies in the treatment of a variety of cancers. Additionally, researchers are working to develop next-generation bispecifics with improved potency, specificity, and reduced immunogenicity. These advances will likely lead to the development of new and more effective treatments for cancer.