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Published on: March 24, 2017
Short synthetic glycopeptides successfully induce antibody responses to carcinoma-associated Tn antigen
S Vichier-Guerre1, R Lo-Man, S Bay
1Unité de Chimie Organique, Institut Pasteur, Paris, France.
Abstract:
Glycopeptides containing a tumor-associated carbohydrate antigen (mono-, tri- or hexa-Tn antigen) as a B-cell epitope and a CD4+ T-cell epitope (PV: poliovirus or TT: tetanus toxin) were prepared for immunological studies. Several Tn antigen residues [FmocSer/Thr (alpha-GalNAc)-OH] were successively incorporated into the peptide sequence with unprotected carbohydrate groups. The tri- and hexa-Tn glycopeptides were recognized by MLS128, a Tn-specific monoclonal antibody. The position of the tri-Tn motif in the peptide sequence and the peptide backbone itself do not alter its antigenicity. As demonstrated by both ELISA and FACS analysis, the glycopeptides induced high titers of anti-Tn antibodies in mice, in the absence of a carrier molecule. In addition, the generated antibodies recognized the native Tn antigen on cancer cells. The antibody response obtained with a D-(Tn3)-PV glycopeptide containing three alpha-GalNAc-D-serine residues is similar that obtained with the Tn6-PV glycopeptide. These results demonstrate that short synthetic glycopeptides are able to induce anticancer antibody responses.
Insights
Short synthetic glycopeptides carrying tumor-associated Tn antigens were developed. These glycopeptides effectively induced anticancer antibodies in mice, recognizing native tumor antigens.
Area of Science:
- Immunology
- Glycobiology
- Cancer Research
Background:
- Tumor-associated carbohydrate antigens (Tn antigens) are crucial in cancer biology.
- Developing effective immunotherapies targeting these antigens remains a challenge.
Purpose of the Study:
- To synthesize glycopeptides containing tumor-associated Tn antigens and T-cell epitopes.
- To evaluate the immunogenicity and antigenicity of these synthetic glycopeptides.
- To assess the potential of these glycopeptides in inducing anticancer antibody responses.
Main Methods:
- Synthesis of glycopeptides with mono-, tri-, and hexa-Tn antigens and T-cell epitopes (poliovirus or tetanus toxin).
- Characterization of glycopeptides using a Tn-specific monoclonal antibody (MLS128).
- Immunization of mice with glycopeptides and analysis of antibody responses using ELISA and FACS.
Main Results:
- Tri- and hexa-Tn glycopeptides were recognized by the MLS128 antibody.
- The position and peptide backbone did not affect antigenicity.
- Glycopeptides induced high titers of anti-Tn antibodies in mice without a carrier.
- Generated antibodies recognized native Tn antigens on cancer cells.
Conclusions:
- Short synthetic glycopeptides can act as potent immunogens.
- These glycopeptides can elicit specific antibody responses against tumor-associated Tn antigens.
- Synthetic glycopeptides represent a promising strategy for developing cancer vaccines and immunotherapies.
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