Phase I study of sequential vaccinations with fowlpox-CEA(6D)-TRICOM alone and sequentially with vaccinia-CEA(6D)-TRICOM, with and without granulocyte-macrophage colony-stimulating factor, in patients with carcinoembryonic antigen-expressing carcinomas.

Abstract

PURPOSE:

Our previous clinical experience with vaccinia and replication-defective avipox recombinant carcinoembryonic antigen (CEA) vaccines has demonstrated safety and clinical activity with a correlation between CEA-specific immune response and survival. Preclinical evidence demonstrated that the addition of the transgenes for three T-cell costimulatory molecules (B7-1, ICAM-1, LFA-3, designated TRICOM) results in a significant improvement in antigen-specific T-cell responses and antitumor activity. We describe here the first trial in humans of the CEA-TRICOM vaccines (also including an enhancer agonist epitope within the CEA gene).

PATIENTS AND METHODS:

Fifty-eight patients with advanced CEA-expressing cancers were accrued to eight cohorts that involved vaccinations with the following: replication-defective fowlpox recombinant (rF)-CEA(6D)-TRICOM; primary vaccination with recombinant vaccinia (rV)-CEA(6D)-TRICOM plus rF-CEA(6D)-TRICOM booster vaccinations; and rV-CEA(6D)-TRICOM and then rF-CEA(6D)-TRICOM, plus granulocyte-macrophage colony-stimulating factor (GM-CSF) with vaccines, or with divided doses of vaccine with GM-CSF. Vaccines were administered every 28 days for six doses and then once every 3 months. Reverting to treatments every 28 days was allowed if patients progressed on the 3-month schedule.

RESULTS:

In this phase I study, no significant toxicity was observed. Twenty-three patients (40%) had stable disease for at least 4 months, with 14 of these patients having prolonged stable disease (> 6 months). Eleven patients had decreasing or stable serum CEA, and one patient had a pathologic complete response. Enhanced CEA-specific T-cell responses were observed in the majority of patients tested.

CONCLUSION:

We demonstrated that the CEA-TRICOM vaccines are safe and can generate significant CEA-specific immune responses, and they seem to have clinical benefit in some patients with advanced cancer.

• Authors: John L Marshall, James L Gulley, Philip M Arlen, Patricia K Beetham, Kwong-Yok Tsang, Rebecca Slack, James W Hodge, Sandra Doren, Douglas W Grosenbach, Jimmy Hwang, Evelyn Fox, Lauretta Odogwu, Susie Park, Dennis Panicali, Jeffrey Schlom
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 23 Issue 4 Pg. 720-31 (Feb 01 2005) ISSN: 0732-183X [Print] United States
• PMID: 15613691 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article)

Chemical References

• B7-1 Antigen
• CD58 Antigens
• Cancer Vaccines
• Carcinoembryonic Antigen
• Immunoglobulin G
• Vaccines, Synthetic
• Intercellular Adhesion Molecule-1
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Adult
• Aged
• Aged, 80 and over
• B7-1 Antigen (genetics)
• CD58 Antigens (genetics)
• Cancer Vaccines (immunology)
• Carcinoembryonic Antigen (immunology)
• Female
• Fowlpox virus (genetics)
• Granulocyte-Macrophage Colony-Stimulating Factor (immunology, therapeutic use)
• Humans
• Immunoglobulin G (blood)
• Intercellular Adhesion Molecule-1 (genetics)
• Male
• Middle Aged
• Neoplasms (immunology, therapy)
• T-Lymphocytes (immunology)
• Vaccination
• Vaccines, Synthetic (immunology)
• Vaccinia virus (genetics)