Mutated anti-cd22 antibodies with increased affinity to...

C - Chemistry – Metallurgy – 12 – N

Patent

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C12N 15/13 (2006.01) A61K 38/16 (2006.01) A61K 39/395 (2006.01) A61K 47/48 (2006.01) C07K 16/28 (2006.01) C07K 16/30 (2006.01) C12N 15/63 (2006.01) G01N 33/53 (2006.01) G01N 33/554 (2006.01) G01N 33/574 (2006.01)

Patent

CA 2461351

Recombinant immunotoxins are fusion proteins composed of the Fv domains of antibodies fused to bacterial or plant toxins. RFB4 (Fv)-PE38 is an immunotoxin that targets CD22 expressed on B cells and B cell malignancies. The present invention provides antibodies and antibody fragments that have improved ability to bind the CD22 antigen of B cells and B cell malignancies compared to RFB4. Immunotoxins made with the antibodies and antibody fragments of the invention have improved cytotoxicity to CD22-expressing cancer cells. Compositions that incorporate these antibodies into chimeric immunotoxin molecules that can be used in medicaments and methods for inhibiting the growth and proliferation of leukemia and lymphoma cells.

Les immunotoxines recombinées sont des protéines de fusion constituées des domaines Fv d'anticorps fusionnés à des toxines bactériennes ou végétales. RFB4 (Fv)-PE38 est une immunotoxine ayant pour cible les CD22 exprimées sur les cellules B et les tumeurs malignes se développant à partir des cellules B. La présente invention concerne des anticorps et des fragments d'anticorps présentant une aptitude améliorée à la liaison à l'antigène CD22 des cellules B et des tumeurs malignes se développant à partir des cellules B, par rapport au RFB4. Les immunotoxines préparées à partir des anticorps ou des fragments d'anticorps de l'invention présentent une cytotoxicité améliorée contre les cellules cancéreuses exprimant des CD22. Par ailleurs, l'invention concerne des compositions qui incorporent ces anticorps à des molécules d'immunotoxines chimères pouvant être utilisées dans des médicaments, ainsi que des méthodes pour inhiber la croissance et la prolifération des cellules leucémiques et lymphoïdes.

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