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Induction of IgM, IgA and IgE Antibodies in Colorectal Cancer Patients Vaccinated with a Recombinant CEA Protein

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Abstract

Purpose

Previous clinical studies have indicated that natural IgM antibodies have the ability to induce apoptosis of tumor cells but IgE and IgA may also mediate tumor cell killing (in addition to IgG). The aim of the study was to analyse induction of IgM, IgA and IgE antibodies in patients vaccinated with the tumor associated antigen CEA.

Methods

Twenty-four resected CRC patients without macroscopic disease were immunized seven times with CEA ± GM-CSF. Four different dose schedules were used over a 12-month period. IgM, IgA and IgE antibody responses against recombinant CEA were determined by ELISA. Patients were monitored immunologically for 36 months and clinically for 147 months.

Results

GM-CSF significantly augmented the anti-CEA response for all three antibody classes. Low dose of CEA tended to induce a higher IgM, IgA or IgE anti-CEA antibody response than higher. Anti-CEA IgA antibodies could lyse CEA positive tumor cells in antibody dependent cellular cytotoxicity (ADCC) as well as in complement dependent cytotoxicity (CDC). A significant correlation between survival and high IgA anti-CEA titers was noted (p = 0.02) irrespective of GM-CSF treatment.

Conclusions

The observation that IgA anti-CEA antibodies were cytotoxic and associated with improved survival might indicate that also these antibodies may exert a clinical anti-tumor effect.

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Abbreviations

CRC:

Colorectal carcinoma

rCEA:

Recombinant carcinoembryonic antigen

GM-CSF:

Granulocyte/monocyte colony stimulating factor

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Acknowledgements

We would like to thank Maggy Magnusson for expert technical assistance and Bo Nilsson for excellent statistical support. Recombinant CEA was a kind gift from Protein Sciences Corp. Meriden, CT, USA. This study was supported by grants from the Swedish Cancer Society, the Cancer Society in Stockholm, the King Gustaf V Jubilee Fund, the Cancer and Allergy Foundation, Torsten and Ragnar Söderberg Foundation, Tornspiran, Hesselman, the Goldi and Ludvig Berglund Foundation, the Research Fund of the Department of Oncology, Uppsala University Hospital, Swedish Medical Society and the Karolinska Institute Foundations.

Disclosures

The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Department of Oncology and CancerCentreKarolinska at the Karolinska Institute, Karolinska University Hospital Solna, SE-171 76, Stockholm, Sweden

    Caroline Staff, Mohammad Hojjat-Farsangi, Szilvia Mosolits, Maria Liljefors, Jan-Erik Frödin & Håkan Mellstedt

  2. Department of Clinical Chemistry, Engelholm Hospital, SE-262 57, Engelholm, Sweden

    Carl G. M. Magnusson

  3. Institute for Infectious Disease Control, Karolinska Institutet, Stockholm, Sweden

    Britta Wahrén

  4. Department of Oncology, Radiology and Radiation Science, Section of Oncology, Uppsala University, SE-751 85, Uppsala, Sweden

    Gustav J. Ullenhag

  5. Department of Oncology (Radiumhemmet), Karolinska University Hospital Solna, Stockholm, Sweden

    Håkan Mellstedt

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  1. Caroline Staff
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Correspondence to Håkan Mellstedt.

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ESM 1

Figure 1S. IgM (A), IgA (B) and IgE (C) anti-CEA antibody responses (median) in CRC patients (n = 24) vaccinated with rCEA in relation to the rCEA dose. Six patients were included in each dose cohort. Arrows indicate immunization times. No statistically significant differences were observed at any time point (Mann–Whitney U-test). Figure 2S. Overall survival of rCEA vaccinated CRC patients in relation to IgA and IgG anti-CEA antibody levels. Solid line indicates patients with IgA as well as IgG anti-CEA antibody levels (through value) above the median (n = 9) and dotted line the remaining patients (n = 15). The difference is statistically significance (p = 0.05) (univariate Wilcoxon Gehan exact life table test). (PDF 133 kb)

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Staff, C., Magnusson, C.G.M., Hojjat-Farsangi, M. et al. Induction of IgM, IgA and IgE Antibodies in Colorectal Cancer Patients Vaccinated with a Recombinant CEA Protein. J Clin Immunol 32, 855–865 (2012). https://doi.org/10.1007/s10875-012-9662-7

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  • DOI: https://doi.org/10.1007/s10875-012-9662-7

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