Adjuvant Postoperative CD40 Agonist and PD-1 Antagonist Combination Therapy in Syngeneic Tongue Cancer Mouse Model.

Abstract

Using a syngeneic tongue cancer mouse model, the effect of CD40 agonist and PD-1 antagonist combination therapy for local recurrence after surgery was evaluated in a partially depleted CD4 model. C3H/HeN mice were injected with 0.05 mg of the anti-mouse CD4 clone GK1.5, causing partial depletion of CD4 cells. Tongue cancer was induced by injecting the squamous cell carcinoma (SCC) VII cell line, the tumor was resected by partial glossectomy, and CD40 agonist and/or PD-1 antagonist therapy was administered postoperatively. Partial depletion of CD4 cells resulted in faster growth of a recurring tumor in the tongue, faster loss of body weight, and decreased number of CD8a-positive cells in the tumor. Postoperative adjuvant therapy with a combination of CD40 agonist and PD-1 antagonist resulted in a significant increase in survival compared to the CD40 agonist single treatment. CD40 agonist and PD-1 antagonist combination therapy could be an effective postoperative adjuvant treatment, especially in cases with decreased CD4 T cell activity.