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Immunogenicity of synthetic TF-KLH (keyhole limpet hemocyanin) and sTn-KLH conjugates in colorectal carcinoma patients

  • Original Article
  • Active Specific Immunotherapy, Adjuvants, Thomsen-Friedenreich(TF), Slalyl-Tn, Keyhole Limpet Hemocyanin, Tumor Vaccine
  • Published:
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Abstract

Mucins of colorectal carcinomas overexpress the cancer-associated disaccharides Thomsen-Friedenreich antigen (TF) and sialyl-Tn antigen (sTn), making these antigens suitable for active specific immunotherapy. Patients at high risk for recurrent colon cancer, but free from disease after surgical resection, were immunized with synthetic TF and sTn covalently attached by a two-carbon crotyl linker to keyhole limpet hemocyanin (KLH). Four groups of patients were treated with TF-KLH without adjuvant, TF-KLH plus the immunological adjuvant Detox, sTn-KLH plus Detox, or sTn-KLH plus the immunological adjuvant QS-21, and the serological response was monitored. Enzyme-linked immunosorbent assay (ELISA), do-blot immunostains, and inhibition assays were used to identify antibody responses against synthetic TF and sTn epitopes and against natural antigens, including asialoglycophorin expressing TF antigen, and ovine submaxillary mucin and the human colon cancer line LS-C expressing sTn antigen. Our results demonstrate that vaccines containing TF or sTn-KLH conjugates plus immunological adjuvants Detox and especially QS-21 induced high IgM and IgG antibody titers against the respective synthetic disaccharide epitopes. However, when tested against natural antigens expressing these disaccharide epitopes, IgM antibodies showed weak to moderate reactivity, while IgG antibodies were almost totally unreactive. On the basis of these results we are continuing to test modifications of synthetic TF and sTn epitopes to identify those that induce IgM and IgG antibodies that are more reactive with these antigens as they are expressed on tumor mucins.

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Authors and Affiliations

  1. Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, 10021, New York, NY, USA

    Sucharita Adluri, Shengle Zhang, Kenneth O. Lloyd & Philip O. Livingston

  2. Mount Sinai Medical Center, 10029, New York, NY, USA

    Shunichiro Ogata & Steven H. Itzkowitz

  3. Active Biotherapies Inc., 10591, Tarrytown, NY, USA

    Fiedhelm Helling

Authors
  1. Sucharita Adluri
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  2. Fiedhelm Helling
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  3. Shunichiro Ogata
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  4. Shengle Zhang
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  5. Steven H. Itzkowitz
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  6. Kenneth O. Lloyd
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  7. Philip O. Livingston
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Additional information

This work was supported by grants from the National Institutes of Health (CA33049, CA52491, CA08748) and the Chemotherapy Foundation

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Adluri, S., Helling, F., Ogata, S. et al. Immunogenicity of synthetic TF-KLH (keyhole limpet hemocyanin) and sTn-KLH conjugates in colorectal carcinoma patients. Cancer Immunol Immunother 41, 185–192 (1995). https://doi.org/10.1007/BF01521345

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  • DOI: https://doi.org/10.1007/BF01521345

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