Targeting lymphoma with precision using semisynthetic anti-idiotype peptibodies.
B-cell lymphomas express a functionally active and truly tumor-specific cell-surface product, the variable region of the B-cell receptor (BCR), otherwise known as idiotype. The tumor idiotype differs, however, from patient to patient, making it a technical challenge to exploit for therapy. We have developed a method of targeting idiotype by using a semisynthetic personalized therapeutic that is more practical to produce on a patient-by-patient basis than monoclonal antibodies. In this method, a small peptide with affinity for a tumor idiotype is identified by screening a library, chemically synthesized, and then affixed to the amino terminus of a premade IgG Fc protein. We demonstrate that the resultant semisynthetic anti-idiotype peptibodies kill tumor cells in vitro with specificity, trigger tumor cell phagocytosis by macrophages, and efficiently clear human lymphoma in a murine xenograft model. This method could be used to target tumor with true precision on a personalized basis.
Department of Medicine, Division of Oncology, Stanford University, Stanford, CA 94305.
James
J
Torchia
Department of Medicine, Division of Oncology, Stanford University, Stanford, CA 94305.
Kipp
K
Weiskopf
Department of Medicine, Division of Oncology, Stanford University, Stanford, CA 94305 levy@stanford.edu.
Ronald
R
Levy
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage* / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D015195:Drug Design; D005260:Female; D006801:Humans; D008223:Lymphoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D015202:Protein Engineering / Q000379:methods*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D014614:Vaccines, Synthetic / Q000008:administration & dosage* / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D019496:Cancer Vaccines; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic
idiotype; lymphoma; peptibody; precision medicine