We report here the production and the properties of single chain Fv fragments (scFvs) derived from the anti-p53 monoclonal antibodies PAb421 and 11D3. 11D3 is a newly generated monoclonal antibody which exhibits properties very comparable to those of PAb421. The scFvs PAb421 and 11D3 are able to stably associate with p53 and to restore the DNA binding activity of some p53 mutants in vitro . When expressed in p53 −/− human tumour cells, the scFv421 is essentially localized in the cytoplasm in the absence of p53, and in the nucleus when exogenous p53 is present. Thus, p53 is also able to stably associate with an anti-p53 scFv in cells. Cotransfection of p53 −/− human tumour cells with expression vectors encoding the His273 p53 mutant and either scFv leads to restoration of the p53 mutant deficient transcriptional activity. These data demonstrate that, in human tumour cells, these scFvs are able to restore a function essential for the tumour suppressor activity of p53 and may represent a novel class of molecules for p53-based cancer therapy.

The design of conditional gene expression systems restricted to given tissues or cellular types is an important issue of gene therapy. Systems based on the targeting of molecules characteristic of the pathological state of tissues would be of interest. We have developed a synthetic transcription factor by fusing a single chain antibody (scFv) directed against p53 with the bacterial tetracycline repressor as a DNA binding domain. This hybrid protein binds to p53 and can interact with a synthetic promoter containing tetracycline-operator sequences. Gene expression can now be specifically achieved in tumor cells harboring an endogenous mutant p53 but not in a wild-type p53 containing tumor cell line or in a non-transformed cell line. Thus, a functional transactivator centered on single chain antibodies can be expressed intracellularly and induce gene expression in a scFv-mediated specific manner. This novel class of transcriptional transactivators could be referred as `trabodies' for transcription-activating-antibodies. The trabodies technology could be useful to any cell type in which a disease related protein could be the target of specific antibodies.

Mice that have been specially bred to lack a protein known as Grf-1, which is normally found only in the brain, do not grow properly after they are born and remain small all their lives. We have now identified a function of Grf-1 as an important regulator of the synthesis and release of growth hormone. Moreover, grf1, the gene encoding this protein, is unlike other imprinted genes that affect growth because it operates after, rather than before, birth.

Biology of the CellVolume 76, Issue 2 p. 229-229 Saccharomyces cerevisiae CDC25 [1028–1589] is a guanine nucleotide exchange factor for mammalian ras proteins and is ongenic in HIH3T3 cells Marie-Christine Chevallier-Multon, Marie-Christine Chevallier-Multon Molecular Oncology Laboratory, C.R.V.A., — I. B. V. — Rhône-Poulenc Rorer, 13 quai Jules Guesde, 94403 Vitry sur Seine Cédex, France.Search for more papers by this authorFabien Schweighoffer, Fabien Schweighoffer Molecular Oncology Laboratory, C.R.V.A., — I. B. V. — Rhône-Poulenc Rorer, 13 quai Jules Guesde, 94403 Vitry sur Seine Cédex, France.Search for more papers by this authorIsabelle Barlat, Isabelle Barlat Molecular Oncology Laboratory, C.R.V.A., — I. B. V. — Rhône-Poulenc Rorer, 13 quai Jules Guesde, 94403 Vitry sur Seine Cédex, France.Search for more papers by this authorNicole Baudouy, Nicole Baudouy Molecular Oncology Laboratory, C.R.V.A., — I. B. V. — Rhône-Poulenc Rorer, 13 quai Jules Guesde, 94403 Vitry sur Seine Cédex, France.Search for more papers by this authorIsabelle Fath, Isabelle Fath Molecular Oncology Laboratory, C.R.V.A., — I. B. V. — Rhône-Poulenc Rorer, 13 quai Jules Guesde, 94403 Vitry sur Seine Cédex, France.Search for more papers by this authorMarc Duchesne, Marc Duchesne Molecular Oncology Laboratory, C.R.V.A., — I. B. V. — Rhône-Poulenc Rorer, 13 quai Jules Guesde, 94403 Vitry sur Seine Cédex, France.Search for more papers by this authorBruno Tocqué, Bruno Tocqué Molecular Oncology Laboratory, C.R.V.A., — I. B. V. — Rhône-Poulenc Rorer, 13 quai Jules Guesde, 94403 Vitry sur Seine Cédex, France.Search for more papers by this author Marie-Christine Chevallier-Multon, Marie-Christine Chevallier-Multon Molecular Oncology Laboratory, C.R.V.A., — I. B. V. — Rhône-Poulenc Rorer, 13 quai Jules Guesde, 94403 Vitry sur Seine Cédex, France.Search for more papers by this authorFabien Schweighoffer, Fabien Schweighoffer Molecular Oncology Laboratory, C.R.V.A., — I. B. V. — Rhône-Poulenc Rorer, 13 quai Jules Guesde, 94403 Vitry sur Seine Cédex, France.Search for more papers by this authorIsabelle Barlat, Isabelle Barlat Molecular Oncology Laboratory, C.R.V.A., — I. B. V. — Rhône-Poulenc Rorer, 13 quai Jules Guesde, 94403 Vitry sur Seine Cédex, France.Search for more papers by this authorNicole Baudouy, Nicole Baudouy Molecular Oncology Laboratory, C.R.V.A., — I. B. V. — Rhône-Poulenc Rorer, 13 quai Jules Guesde, 94403 Vitry sur Seine Cédex, France.Search for more papers by this authorIsabelle Fath, Isabelle Fath Molecular Oncology Laboratory, C.R.V.A., — I. B. V. — Rhône-Poulenc Rorer, 13 quai Jules Guesde, 94403 Vitry sur Seine Cédex, France.Search for more papers by this authorMarc Duchesne, Marc Duchesne Molecular Oncology Laboratory, C.R.V.A., — I. B. V. — Rhône-Poulenc Rorer, 13 quai Jules Guesde, 94403 Vitry sur Seine Cédex, France.Search for more papers by this authorBruno Tocqué, Bruno Tocqué Molecular Oncology Laboratory, C.R.V.A., — I. B. V. — Rhône-Poulenc Rorer, 13 quai Jules Guesde, 94403 Vitry sur Seine Cédex, France.Search for more papers by this author First published: 1992 https://doi.org/10.1016/0248-4900(92)90288-CAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume76, Issue21992Pages 229-229 RelatedInformation