The variable region of the B cell receptor (BCR), known as the idiotype, is a patient-specific tumour surface marker on lymphoma cells. To therapeutically target idiotypes, Torchia et al. created antibody-like molecules termed peptibodies comprised of a short synthetic patient-specific idiotype-binding peptide covalently linked to the amino-terminus of a recombinant immunoglobulin G crystallizable fragment (IgG Fc). The peptibodies crosslink idiotypes on human lymphoma cells, triggering BCR signalling and inducing apoptosis, resulting in complete clearance of human lymphoma in mouse xenograft models.
References
Torchia, J. et al. Targeting lymphoma with precision using semisynthetic anti-idiotype peptibodies. PNAS 113, 5376–5381 (2016)
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Crunkhorn, S. Peptibodies rescue mice from lymphoma. Nat Rev Drug Discov 15, 384 (2016). https://doi.org/10.1038/nrd.2016.103
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DOI: https://doi.org/10.1038/nrd.2016.103