title: Phase I trial of a recombinant yeast-CEA vaccine (GI-6207) in adults with metastatic CEA-expressing carcinoma.
abstract: 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.
authors: Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors: Marijo
authors: M
authors: Bilusic
authors: Christopher R
authors: CR
authors: Heery
authors: Philip M
authors: PM
authors: Arlen
authors: Myrna
authors: M
authors: Rauckhorst
authors: David
authors: D
authors: Apelian
authors: Kwong Y
authors: KY
authors: Tsang
authors: Jo A
authors: JA
authors: Tucker
authors: Caroline
authors: C
authors: Jochems
authors: Jeffrey
authors: J
authors: Schlom
authors: James L
authors: JL
authors: Gulley
authors: Ravi A
authors: RA
authors: Madan
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000378:metabolism; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005500:Follow-Up Studies; D005818:Genetic Engineering; D005822:Genetic Vectors; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000627:therapeutic use*
chemical_list: D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D016207:Cytokines; D019444:Vaccines, DNA; C588090:yeast-CEA vaccine