Humanized anti-CD4 antibody (IT1208): solid tumor project

• Transient depletion of CD4 cells from tumor-bearing mice leads to tumor-specific CD8 cell activation and proliferation, resulting of infiltration into the tumor of CD8 cells with anti-tumor activity.
• Combination of CD4 depletion with immune checkpoint antibodies results in synergistic anti-tumor efficacy in several mouse tumor models.
• Because treatment induces CD8 proliferation, efficacy can be assessed using blood tests, without the need for tissue biopsies.
• Anti-CD4 treatment ameliorates the adverse effects (e.g. autoimmune-like diseases) caused by immune checkpoint blockade.
• A physician-driven phase I clinical trial currently underway with the support of AMED.

Humanized anti-CD4 (IT1208): GVHD project

• Although allo-HSCT is the only treatment option for hematological malignancies, it can result in adverse effects such as severe GVHD.
• Depletion of donor CD4 T cells provides a way to avoid both leukemia-related mortality as well as GVHD-related mortality.
• We have reproduced this phenomenon in a humanized mouse model with a humanized anti-CD4 antibody.
• Planning is underway for a GVHD clinical trial based on the results of a phase I clinical trial in solid tumors.