Targeting lymphoma with precision using semi-synthetic anti-idiotype peptibodies

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Abstract/Contents

Abstract
B-cell lymphomas express a functionally active and truly tumor-specific cell-surface product, the variable region of the B-cell receptor, otherwise known as idiotype. The tumor idiotype differs from patient to patient, however, making it a technical challenge to exploit for therapy. We have developed a method of targeting idiotype using a semi-synthetic 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 pre-made IgG Fc protein. We demonstrate that the resultant semi-synthetic 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. Our results suggest that this method could be used to target tumor with true precision on a personalized basis.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2015
Issuance monographic
Language English

Creators/Contributors

Associated with Torchia, James Anthony
Associated with Stanford University, Interdepartmental Program in Immunology.
Primary advisor Levy, Ronald, 1941 December 6-
Thesis advisor Levy, Ronald, 1941 December 6-
Thesis advisor Alizadeh, Ash
Thesis advisor Weissman, Irving L
Advisor Alizadeh, Ash
Advisor Weissman, Irving L

Subjects

Genre Theses

Bibliographic information

Statement of responsibility James Torchia.
Note Submitted to the Interdepartmental Program in Immunology.
Thesis Thesis (Ph.D.)--Stanford University, 2015.
Location electronic resource

Access conditions

Copyright
© 2015 by James Anthony Torchia
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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