Immunogenicity of protein therapeutics

led by Sébastien Lacroix-Desmazes

We investigate why some drug generate an immune response and we elaborate strategies to avoid or prevent it.

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We use therapeutic pro-coagulant factor VIII (FVIII) as a model to understand the immunogenicity of protein therapeutics. About 30% of patients with hemophilia A develop neutralizing Abs against therapeutic FVIII. We wish to dissect the interactions of FVIII with the immune system, and to decipher the state of central and peripheral tolerance to FVIII in health and disease together with the mechanisms underlying immune tolerance induction. We also develop novel strategies to prevent the onset of the anti-FVIII immune response, for instance by inducting materno-fetal tolerance using Fc-fused FVIII constructs, controlling memory B cells using immuno-suppressive drugs, or optimizing FVIII-derived molecules for induction of oral tolerance.