CEA peptide 1-6D

CEA peptide 1-6D, also known as CAP1-6D, is a modified peptide derived from carcinoembryonic antigen (CEA). It's a 9-amino acid sequence (YLSGADLNL) that represents an altered peptide ligand of the CAP1 epitope from human CEA. This peptide was developed to enhance immunogenicity and break T cell tolerance to CEA, which is overexpressed in many cancers including colorectal, pancreatic, and some lung and breast cancers[1][4]. ## Mechanism of Action CEA peptide 1-6D functions as an immunostimulant by enhancing recognition by T cell receptors without changing binding to HLA-A2. The peptide contains a heteroclitic mutation that changes asparagine to aspartic acid at position 6, which significantly improves its ability to sensitize cytotoxic T lymphocytes (CTLs)[4][6]. This modification makes it 100-1000 times more effective at inducing CEA-specific immune responses compared to the native CAP1 peptide[4][8]. When used in vaccines, CEA peptide 1-6D elicits cytotoxic T lymphocyte immune responses against CEA-expressing tumors. Clinical trials have shown that it can induce dose-dependent T cell responses in cancer patients, with higher doses (1 mg) producing the most robust responses[6]. ## Clinical Development The peptide has been investigated in several clinical trials: 1. A randomized phase I trial in pancreatic cancer patients evaluated different doses (10 μg, 100 μg, and 1000 μg) of the peptide emulsified in Montanide adjuvant with GM-CSF[2][6]. 2. The National Cancer Institute conducted Phase 1 trials for refractory cancer and solid tumors using this peptide[1]. 3. A phase 1/2 clinical trial evaluated the peptide in metastatic colorectal cancer patients, showing minimal toxicity and the ability to induce CEA-specific immune responses despite pre-existing immunity to the delivery vector[4]. The peptide has shown promising results in generating immune responses against CEA-expressing tumors, with some patients experiencing extended survival. In one trial, 48% of metastatic colorectal cancer patients were still alive at 12 months[4]. CEA peptide 1-6D represents an important advancement in cancer immunotherapy, particularly for targeting CEA-expressing malignancies that have traditionally been difficult to treat with conventional approaches.

Other names

CAP1-6DCAP-1-6DCAP 1-6DYLSGADLNLhuman carcinoembryonic antigen peptide 16D