Selective killing and diagnosis of p53+ neoplastic cells

Details Selective killing and diagnosis of p53+ neoplastic cells Selective killing and diagnosis of p53+ neoplastic cells

C - Chemistry, Metallurgy

12

N

C12N 15/86 (2006.01) A61K 35/76 (2006.01) A61K 48/00 (2006.01) C12N 7/04 (2006.01) C12Q 1/68 (2006.01) G01N 33/50 (2006.01) G01N 33/574 (2006.01)

Patent

CA 2309555

Methods and compositions for treating and diagnosing neoplastic disease using viruses are provided. Preferably, mutant adenovirus lacking viral proteins which bind and/or inactivate p53 are administered to a patient having a neoplasm which comprises cells exhibiting p53 and lacking, or substantially devoid of mismatch repair activity. The mutant virus is able to substantially produce a replication phenotype in such neoplastic cells but is substantially unable to produce a replication phenotype in non-replicating, non-neoplastic cells having essentially normal p53 function. The preferential generation of a replication phenotype in neoplastic cells results in a preferential killing of the neoplastic cells, either directly or by expression of a cytotoxic gene in cells expressing a viral replication phenotype.

Procédés et compositions pour le traitement et le diagnostic de maladies néoplasiques, au moyen de virus. De préférence, des adénovirus mutants exempts de protéines virales qui fixent et/ou inactivent p53, sont administrés à un patient souffrant d'une tumeur comprenant des cellules comportant p53 et exemptes, ou sensiblement dénuées sensiblement d'activité de réparation de mésappariement. Le virus mutant est capable de sensiblement produire un phénotype de réplication dans lesdites cellules néoplasiques, mais il est sensiblement incapable de produire un phénotype de réplication dans les cellules non néoplasiques et non répliquantes, ayant une fonction p53 sensiblement normale. La génération préférée d'un phénotype de réplication dans les cellules néoplasiques induit la destruction préférentielle des cellules néoplasiques, soit directement, soit par l'expression d'un gène cytotoxique dans des cellules exprimant un phénotype de réplication viral.

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