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Therapeutic antibodies to ganglioside GD2 evolved from highly selective germline antibodies

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Bos taurus Dermestes lardarius Mus musculus Sus scrofa domesticus Human immunodeficiency virus 1 Homo sapiens unidentified Trypanosoma cruzi Oryctolagus cuniculus Ovis aries Frangula alnus Gossypium hirsutum Pachymenia carnosa Rhodotorula Ceratonia siliqua Quercus alba Pandalus borealis Senegalia senegal Megathura crenulata Gallus gallus Bothrops moojeni Oncorhynchus nerka

PROVIDER: GSE100438 | GEO | 2017/08/25

SECONDARY ACCESSION(S): PRJNA391729

REPOSITORIES: GEO

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Therapeutic antibodies to ganglioside GD2 evolved from highly selective germline antibodies V

Project description:Purpose: This study uses a high-throughput glycan microarray to evaluate the immunological evolution of antibodies to the glyco-antigen GD2. The goal is to determine germline and affinity mature antibody specificity and affinities/ Results: Affinity mature anti-GD2 antibodies 3F8 and ch14.18 had high affinity and were highly specific for the target GD2. Germline antibodies were also hihgly specific and had surprisingly high affinity. Conclusion: Antibodies to GD2 evolved from highly specific germlines. Highly specific germlines may be critical in evading autoimmunity issues.

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Therapeutic antibodies to ganglioside GD2 evolved from highly selective germline antibodies IV

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Therapeutic antibodies to ganglioside GD2 evolved from highly selective germline antibodies III

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Therapeutic antibodies to ganglioside GD2 evolved from highly selective germline antibodies II

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Therapeutic antibodies to ganglioside GD2 evolved from highly selective germline antibodies I

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Therapeutic antibodies to ganglioside GD2 evolved from highly selective germline antibodies VII

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Therapeutic antibodies to ganglioside GD2 evolved from highly selective germline antibodies VI

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

Project description: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.

| S-EPMC5572838 | biostudies-literature