A trial of vaccination with the carcinoembryonic antigen (CEA) peptide CAP 1–6D with montanide ISA 51 adjuvant or granulocyte- macrophage colony stimulating factor (GM-CSF) in HLA-A2+ patients with CEA producing adenocarcinomas of gastrointestinal (GI) track

Abstract

13513 Advances in drug therapy have improved the survival of patients with GI tumors but most patients with metastatic disease are not cured. Immunotherapy is an additional modality of treatment. In this trial, the CEA peptide, CAP 1–6D, was combined with either GM-CSF or montanide ISA 51 as adjuvants and used to vaccinate patients with CEA producing GI tumors. End points were development of peptide responsive immunity, toxicity, and anti-tumor effects. To be eligible, patients were required to have a histologic diagnosis of adenocaricnoma of GI tract origin with a life expectancy of at least 6 months and to have either metastatic disease or to have completed standard adjuvant therapy after resection. Patients were required to have a CEA producing tumor, be HLA-A2 positive, have a performance status of 0–1, test negative for HIV, hepatitis B and C, and have adequate bone marrow, liver and kidney function. Treatment consisted of 1 mg of CAP 1–6D peptide combined with either 250 ug of GM-CSF given intradermally, or 2 ml of Montanide ISA 51 given subcutaneously every 3 weeks for 6 treatments. Blood was drawn for ELISpot assay at each visit. Nine (out of a planned 10) patients, 8 with colorectal cancer and 1 with pancreatic cancer, were entered before the peptide was deemed expired and withdrawn from clinical use by the NCI. Of five colorectal patients with metastatic disease at baseline 4 progressed and 1 had stable disease. The pancreatic cancer patient was treated adjuvantly but progressed during therapy. Three colorectal cancer patients treated adjuvantly were free of disease at baseline and at the completion of therapy. Treatments were well tolerated. ELISpot data on 5 patients showed that 4 patients developed peptide responsive immunity. Responsive patients included those receiving either GM-CSF or Montanide ISA 51 and both adjuvantly treated and progressive metastatic colorectal patients and the progressed pancreatic cancer patient. This vaccine regimen can be safely given to cancer patients and can produce peptide responsive immunity in the ELISpot assay but this does not correlate with clinical anti-tumor effect. No significant financial relationships to disclose.