Immunogenicity of protein therapeutics

Groot, Anne S. De; Scott, David W.

doi:10.1016/j.it.2007.07.011

Cited by 443 publications

(325 citation statements)

References 64 publications

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“…However, they were slightly less recognized by an anti-MUC6 sera, probably because the GalNAc residues reduce the accessibility of antibodies to the protein core. This would be in agreement with previous reports demonstrating that glycosylation interferes with antibody binding (51).…”

Section: Discussionsupporting

confidence: 94%

Tn Glycosylation of the MUC6 Protein Modulates Its Immunogenicity and Promotes the Induction of Th17-biased T Cell Responses

Freire

Lo‐Man

Bay

et al. 2011

Journal of Biological Chemistry

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The Tn antigen (␣-GalNAc-O-Ser/Thr) is one of the most specific human cancer-associated structures. This antigen, together with mucins, the major carriers of O-glycosylated tumor antigens in adenocarcinomas, are being evaluated as anticancer immunotherapeutic targets. In particular, the MUC6 protein, which is normally expressed only in gastric tissues, has been detected in intestinal, pulmonary, colorectal, and breast carcinomas. To develop anti-cancer vaccines based on the Tn antigen, we produced MUC6 proteins with different Tn density by using mixtures of recombinant ppGalNAc-T1, -T2, and -T7. The obtained glycoproteins were characterized and analyzed for their immunological properties, as compared with the non-glycosylated MUC6. We show that these various MUC6:Tn glycoproteins were well recognized by both MUC6 and Tn-specific antibodies. However, Tn glycosylation of the MUC6 protein strongly affected their immunogenicity by partially abrogating Th1 cell responses, and promoting IL-17 responses. Moreover, the non-glycosylated MUC6 was more efficiently presented than MUC6:Tn glycoproteins to specific T CD4 ؉ hybridomas, suggesting that Tn glycosylation may affect MUC6 processing or MHC binding of the processed peptides. In conclusion, our results indicate that Tn glycosylation of the MUC6 protein strongly affects its B and T cell immunogenicity, and might favor immune escape of tumor cells.

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Section: Discussionsupporting

confidence: 94%

Tn Glycosylation of the MUC6 Protein Modulates Its Immunogenicity and Promotes the Induction of Th17-biased T Cell Responses

Freire

Lo‐Man

Bay

et al. 2011

Journal of Biological Chemistry

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“…However, their efficacy can be dramatically compromised by the development of anti-therapeutic protein responses [1,2]. Anti-therapeutic antibodies have the potential to neutralize clinical effects of this class of therapeutics.…”

Section: Basis Of Therapeutic Protein Immunogenicitymentioning

confidence: 99%

Immunogenicity of Therapeutic Fusion Proteins: Contributory Factors and Clinical Experience

Jawa

Cousens

Groot

2013

Fusion Protein Technologies for Biopharmaceuticals

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“…Monoclonal antibody therapeutics have proven to be enormously successful for many hard-to-treat diseases, many of which involve PPIs (Chan and Carter 2010). However, they come with several limitations and liabilities, including cost of goods, convenience of administration, potential side effects, and eventual loss of efficacy due to the production of anti-drug antibodies (De Groot and Scott 2007;Hansel et al 2010). The slow clearance of immunosuppressive monoclonals (basiliximab half-life is~7 days) is advantageous from a dosing perspective, but highly problematic in the event of opportunistic infection or adverse reaction.…”

Section: Allograft Transplantationmentioning

confidence: 99%