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

Cancer Immunol Immunother. 2014 Mar;63(3):225-34. doi: 10.1007/s00262-013-1505-8. Epub 2013 Dec 7.


Yeast-CEA (GI-6207) is a therapeutic cancer vaccine genetically modified to express recombinant carcinoembryonic antigen (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 and 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 0-2, and no history of autoimmunity. Restaging scans were performed at 3 months and then bimonthly. Peripheral blood was collected for the 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 39-81). 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 pre-treated patient population. Further studies are required to determine the clinical benefit of yeast-CEA vaccination.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / therapy*
  • Adult
  • Aged
  • Aged, 80 and over
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cancer Vaccines / therapeutic use*
  • Carcinoembryonic Antigen / genetics
  • Carcinoembryonic Antigen / immunology*
  • Carcinoembryonic Antigen / therapeutic use
  • Cells, Cultured
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / therapy*
  • Cytokines / metabolism
  • Enzyme-Linked Immunospot Assay
  • Female
  • Follow-Up Studies
  • Genetic Engineering
  • Genetic Vectors
  • Humans
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Saccharomyces cerevisiae / genetics*
  • T-Lymphocytes, Regulatory / immunology*
  • Treatment Outcome
  • Vaccines, DNA / therapeutic use*


  • Cancer Vaccines
  • Carcinoembryonic Antigen
  • Cytokines
  • Vaccines, DNA
  • yeast-CEA vaccine