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Durable carcinoembryonic antigen (CEA)-specific humoral and cellular immune responses in colorectal carcinoma patients vaccinated with recombinant CEA and granulocyte/macrophage colony-stimulating factor.
Department of Oncology, Radiology and Clinical Immunology, Section of Oncology, Uppsala University Hospital, Uppsala, Sweden.
Department of Oncology and CancerCentre Karolinska, Karolinska Hospital, Stockholm, Sweden.
Department of Oncology and CancerCentre Karolinska, Karolinska Hospital, Stockholm, Sweden. Department of Immunology, Monoclonal Antibody Research Center, Avesina Research Center, Tehran, Iran.
Department of Surgery, Huddinge University Hospital, Stockholm, Sweden.
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2004 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 10, no 10, 3273-3281 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: Previous studies have indicated that carcinoembryonic antigen (CEA) might be a suitable immunotherapeutic target in colorectal carcinoma (CRC). The aim of the present study was to analyze the immunological and clinical effects of vaccination with CEA together with the adjuvant granulocyte/macrophage colony-stimulating factor (GM-CSF).

EXPERIMENTAL DESIGN: Twenty-four resected CRC patients without macroscopic disease were immunized seven times with recombinant CEA at four different dose levels over a 12-month period. Half of the patients received GM-CSF (80 microg/day for 4 consecutive days) at each immunization. Patients were monitored immunologically for 36 months and clinically for 76 months. T-cell response was evaluated by a [(3)H]thymidine incorporation assay, and IgG response was determined by ELISA.

RESULTS: Minor local side effects were common. All 12 patients (100%) in the GM-CSF group developed a CEA-specific T-cell as well as an IgG response. The corresponding figures in the CEA alone group were 9 of 12 (75%) and 8 of 12 (66%), respectively. GM-CSF significantly augmented the amplitude of the T-cell response and the IgG titers. No dose-response relationship was noted. The immune responses at 12 months persisted 24 months after the last vaccination. Anti-CEA IgG titers were associated with increased survival (P < 0.05), whereas standard prognostic factors had no relationship, with the exception of serum CEA value.

CONCLUSIONS: Vaccination with recombinant CEA and GM-CSF appears to be a nontoxic regimen inducing potent and durable antigen-specific IgG and T-cell response. The results of this study justify more extensive trials with recombinant CEA protein for immunotherapy of CRC.

Place, publisher, year, edition, pages
2004. Vol. 10, no 10, 3273-3281 p.
Keyword [en]
CEA, carcinoembryonic antigen, CRC, colorectal carcinoma, GM-CSF, granulocyte, macrophage, colony-stimulating factor
National Category
Surgery
Identifiers
URN: urn:nbn:se:umu:diva-126904DOI: 10.1158/1078-0432.CCR-03-0706PubMedID: 15161680OAI: oai:DiVA.org:umu-126904DiVA: diva2:1038822
Available from: 2016-10-20 Created: 2016-10-20 Last updated: 2016-10-20

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