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

• Published in: Cancer Immunology, Immunotherapy Immunotherapy, 2014-03, Vol.63 (3), p.225-234
• Main Authors: Bilusic, Marijo, Heery, Christopher R., Arlen, Philip M., Rauckhorst, Myrna, Apelian, David, Tsang, Kwong Y., Tucker, Jo A., Jochems, Caroline, Schlom, Jeffrey, Gulley, James L., Madan, Ravi A.
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - immunology; Adenocarcinoma - therapy; Adult; Aged; Aged, 80 and over; Antigens; Antitumor activity; Autoimmunity; Cancer Research; Cancer vaccines; Cancer Vaccines - therapeutic use; Carcinoembryonic antigen; Carcinoembryonic Antigen - genetics; Carcinoembryonic Antigen - immunology; Carcinoembryonic Antigen - therapeutic use; Carcinoma; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cells, Cultured; Colonic Neoplasms - immunology; Colonic Neoplasms - therapy; Cytokines - metabolism; Enzyme-linked immunosorbent assay; Enzyme-Linked Immunospot Assay; Female; Follow-Up Studies; Genetic Engineering; Genetic Vectors; Humans; Immunology; Immunoregulation; Inflammation; Injections, Subcutaneous; Lymphocytes T; Male; Medicine; Medicine & Public Health; Metastases; Metastasis; Middle Aged; Neoplasm Metastasis; Oncology; Original Article; Patients; Peripheral blood; Population studies; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; T-Lymphocytes, Regulatory - immunology; Thyroid; Thyroid cancer; Toxicity; Treatment Outcome; Tumors; Vaccination; Vaccines; Vaccines, DNA - therapeutic use
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-013-1505-8

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.