Internal medicine

Receptor

Limiting

Immunotherapy

Agonist

Cancer immunotherapy

Monoclonal antibody

Biology

Cancer

Psychiatry

Engineering

Cytotoxic T cell

Agonistic behaviour

Antibody

In vitro

Immunology

Aggression

CD40

Potency

Toxicity

Cancer research

Biochemistry

Medicine

Mechanical engineering

Immune system

Frontiers in Immunology

The clinical use of anti-CD40 agonist monoclonal antibodies (mAbs) is aimed at recruiting the immune system to fight the tumor cells. This approach has been demonstrated to be effective in various preclinical models. However, human CD40 Abs displayed only modest antitumor activity in cancer patients, characterized by low efficacy and dose-limiting toxicity. While recent studies highlight the importance of engineering the Fc region of human CD40 mAbs to optimize their agonistic potency, toxicity remains the main limiting factor, restricting clinical application to suboptimal doses. Here, we discuss the current challenges in realizing the full potential of CD40 mAbs in clinical practice, and describe novel approaches designed to circumvent the systemic toxicity associated with CD40 agonism.

Next Generation CD40 Agonistic Antibodies for Cancer Immunotherapy