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Targeted cytokine delivery to neuroblastoma.



Targeted cytokine delivery to neuroblastoma Biochemical Society Transactions (2002) Volume 30, part 4 ability to cleave this mutant antibody not only at 236 peptide bond, which is the specific cleavage 4 5 6 7 227-228 but also at or close to the Pro-235-Thr- site in wild-type IgAl for type 2 IgAl proteases of N . meningitidis and H. influenzae. References I 2 3 Plaut, A. G. ( I 983) Annu. Rev. Microbiol. 37, 603-622 Senior, B. W. Loomes, L. M. and Kerr, M. A. ( I99 I ) Rev. Med. Microbiol. 2, 200-207 Kilian, M., Reinholdt, I., Lornholt, H., Poulsen, K. and Plaut, A. G., Genco, R. J. and Tomasi, Jr, T. B. ( I 974) J. Immunol. I 13, 289-29 I Gilbert, J. V., Plaut, A. G. and Wright, A. ( I 99 I ) Infect. Immunity 59, 7- I7 Poulsen, K., Reinholdt, J. and Kilian, M. ( I 996) Infect. Immunity 64, 3957-3966 Poulsen, K., Reinholdt, J,, Jespengaard, C., Boye, K., Brown, T. A., Hauge, M. and Kilian, M. (1998) Infect. Immunity 66, I8 1 - 1 90 Frandsen, E. V. G. (1996) Ada Pathol. Microbiol. Immunol. Scand. 104, 321-338 Received I0 April 2002 Targeted cytokine delivery to neuroblastoma P. K. Dehal', M. J. Embleton, J. T. Kernshead and R. E. Hawkins' Medical Oncology, Patenon Institute for Cancer Research, Wilmslow Road, Withington, Manchester M20 4BX, U.K. Abstract The aim of this study was to construct a fusion protein from the cytokine granulocyte/macro- phage colony-stimulating factor (GM-CSF) and a single-chain Fv fragment (scFv D29) and to investigate its potential to activate cells of the immune system against neuroblastoma cells ex- pressing neural cell adhesion molecule (NCAM). Mammalian cell expression of the scFv D29- GM-CSF fusion protein was compared using a number of vectors, including retroviral and adenoviral vectors. The resultant fusion protein, expressed by HeLa cells, was found by ELISA to bind immobilized recombinant NCAM. More- over, FACS analysis confirmed binding to the human neurobla

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