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

Ng, P.P.; Jia, M.; Patel, K.G.; Brody, J.D.; Swartz, J.R.; Levy, S.; Levy, R.

Proceedings of the National Academy of Sciences of the United States of America 109(36): 14526-14531

2012


ISSN/ISBN: 1091-6490
PMID: 22875703
DOI: 10.1073/pnas.1211018109
Accession: 051282624

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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