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Cell Rep. 2017 Aug 15;20(7):1681-1691. doi: 10.1016/j.celrep.2017.07.050.

Therapeutic Antibodies to Ganglioside GD2 Evolved from Highly Selective Germline Antibodies.

Author information

1
Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
2
Basic Science Program, Chemical Biology Laboratory, Leidos Biomedical Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
3
Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. Electronic address: gildersj@mail.nih.gov.

Abstract

Antibodies play a crucial role in host defense and are indispensable research tools, diagnostics, and therapeutics. Antibody generation involves binding of genomically encoded germline antibodies followed by somatic hypermutation and in vivo selection to obtain antibodies with high affinity and selectivity. Understanding this process is critical for developing monoclonal antibodies, designing effective vaccines, and understanding autoantibody formation. Prior studies have found that antibodies to haptens, peptides, and proteins evolve from polyspecific germline antibodies. The immunological evolution of antibodies to mammalian glycans has not been studied. Using glycan microarrays, protein microarrays, cell binding studies, and molecular modeling, we demonstrate that therapeutic antibodies to the tumor-associated ganglioside GD2 evolved from highly specific germline precursors. The results have important implications for developing vaccines and monoclonal antibodies that target carbohydrate antigens. In addition, they demonstrate an alternative pathway for antibody evolution within the immune system that is distinct from the polyspecific germline pathway.

KEYWORDS:

GD2; antibody evolution; ganglioside; germline antibody; glycan microarray

PMID:
28813678
PMCID:
PMC5572838
DOI:
10.1016/j.celrep.2017.07.050
[Indexed for MEDLINE]
Free PMC Article

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