DHODH inhibitor + anti-PD-1 + peptide vaccine

**DHODH inhibitor + anti-PD-1 + peptide vaccine** is an investigational cancer immunotherapy combination designed to enhance antitumor immune responses through complementary mechanisms. **DHODH inhibitors** (e.g., brequinar or teriflunomide) deplete pyrimidine nucleotides, upregulating antigen processing and presentation genes (APP) and MHC class I expression on tumor cells to improve T-cell recognition.[3][4][5] **Anti-PD-1 antibodies** (e.g., nivolumab) block the PD-1/PD-L1 checkpoint to reactivate exhausted T cells.[1][2] **Peptide vaccines** target tumor-associated antigens or immune checkpoints like PD-L1/IDO to stimulate specific T-cell responses, often with adjuvants like Montanide.[1][2] Preclinical studies show DHODH inhibition synergizes with anti-PD-1 (and anti-CTLA-4) in melanoma models by boosting MHC-I and immune infiltration, while clinical trials test anti-PD-1 + peptide vaccines in melanoma.[1][3][5] No specific trial combines all three, but rationale exists for triple therapy in immunotherapy-resistant cancers.