Phase I trial of a recombinant yeast-CEA vaccine (GI-6207) in adults with metastatic CEA-expressing carcinoma

Yeast-CEA (GI-6207) is a therapeutic cancer vaccine genetically modified to express recombinant CEA protein, using heat-killed yeast (Saccharomyces cerevisiae) as a vector. In preclinical studies, yeast-CEA induced a strong immune response to CEA and antitumor responses. Patients received subcutaneous vaccines every 2 weeks for 3 months, then monthly. Patients were enrolled at 3 sequential dose levels: 4, 16, and 40 yeast units (10(7) yeast particles/unit). Eligible patients were required to have serum CEA > 5 ng/mL or > 20% CEA(+) tumor block, ECOG PS 0 to 2, and no history of autoimmunity. Restaging scans were performed at 3 months, then bimonthly. Peripheral blood was collected for analysis of immune response (e.g., by ELISPOT assay). Twenty-five patients with metastatic CEA-expressing carcinomas were enrolled. Median patient age was 52 (range, 39 to 81). A total of 135 vaccines were administered. The vaccine was well tolerated and the most common adverse event was grade 1/2 injection-site reaction. Five patients had stable disease beyond 3 months (range: 3.5-18 months) and each had CEA stabilization while on-study. Some patients showed evidence post-vaccination of increases in antigen-specific CD8(+) T cells and CD4(+) T lymphocytes and decreases in regulatory T cells. Of note, a patient with medullary thyroid cancer had substantial T-cell responses and a vigorous inflammatory reaction at sites of metastatic disease. Yeast-CEA vaccination had minimal toxicity and induced some antigen-specific T-cell responses and CEA stabilization in a heterogeneous, heavily pretreated patient population. Further studies are required to determine the clinical benefit of yeast-CEA vaccination