Article

A vaccine directed to B cells and produced by cell-free protein synthesis generates potent antilymphoma immunity

Division of Oncology, Department of Medicine, Stanford University Medical Center, and Departments of Chemical Engineering and Bioengineering, Stanford University, Stanford, CA 94305.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 08/2012; 109(36):14526-31. DOI: 10.1073/pnas.1211018109
Source: PubMed

ABSTRACT Clinical studies of idiotype (Id) vaccination in patients with lymphoma have established a correlation between the induced anti-Id antibody responses and favorable clinical outcomes. To streamline the production of an Id vaccine, we engineered a small diabody (Db) molecule containing both a B-cell-targeting moiety (anti-CD19) and a lymphoma Id. This molecule (αCD19-Id) was designed to penetrate lymph nodes and bind to noncognate B cells to form an antigen presentation array. Indeed, the αCD19-Id molecule accumulated on B cells in vivo after s.c. administration. These noncognate B cells, decorated with the diabody, could then stimulate the more rare Id-specific B cells. Peptide epitopes present in the diabody linker augmented the response by activating CD4(+) helper T cells. Consequently, the αCD19-Id molecule induced a robust Id-specific antibody response and protected animals from tumor challenge. Such diabodies are produced in a cell-free protein expression system within hours of amplification of the specific Ig genes from the B-cell tumor. This customized product can now be available to vaccinate patients before they receive other, potentially immunosuppressive, therapies.

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