Scientists, Relying on Work from 1980s, Develop a Molecule Seen to Kill B-cell Lymphoma in Mice

Scientists, Relying on Work from 1980s, Develop a Molecule Seen to Kill B-cell Lymphoma in Mice

Stanford University researchers developed a new method, using molecules called peptibodies, to target and clear human lymphoma cells in a mouse model. The approach is a refinement of a quite promising monoclonal antibody that was developed over 30 years ago, but discontinued due to high production costs.

The study, “Targeting lymphoma with precision using semisynthetic anti-idiotype peptibodies,” was published in the Proceedings of the National Academy of Sciences.

B-cell lymphomas express a tumor-specific cell-surface product, the idiotype, which differs in each patient, a characteristic that renders it difficult to target therapeutically. Researchers developed semisynthetic personalized peptides with an affinity for patient-specific tumor idiotypes. These products are identified by screening a library, and then chemically synthesized and bound to an antibody base, giving rise to “hybrid” molecules named peptibodies. These new molecules were derived from an earlier monoclonal antibody, whose production and clinical development was funded by Idec Pharmaceuticals. The antibody was seen to target malignant B-cells involved in the development of lymphoma and, in some instances, destroy human lymphoma in mouse models, and showed promise in early clinical trials. Idec decided at the time, however, to discontinue development efforts because the antibody’s high production costs made its wide use unlikely.

The peptibodies were developed by James Torchia, Kipp Weiskopf and Ronald Levy, a physician-researcher who had developed the original monoclonal antibody with colleagues decades ago. The three researchers demonstrated that these hybrid peptibodies, cheaper to produce on a patient-by-patient basis than the monoclonal antibody, were able to kill tumor cells in vitro in a specific manner, and trigger tumor cell phagocytosis by macrophages and clear human B-cell lymphomas in mouse models of the disease.

Importantly, the drug does not seem to affect healthy B cells, unlike the drug Rituxan, the first approved monoclonal antibody for cancer, also developed by Idec and first commercialized in 1997.

Researchers believe this method can target tumors on a patient-specific specific fashion, without the toxicities and immunosupression associated with current standard-of-care therapies, and hope to start clinical trials on this new promising therapy within a year.

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