Methods of therapy for cancers expressing the cd40 antigen

A - Human Necessities – 61 – K

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A61K 39/395 (2006.01) A61K 38/20 (2006.01) A61P 35/02 (2006.01)

Patent

CA 2544948

Methods of treating a subject for a cancer comprising neoplastic cells expressing the CD40 cell surface antigen are provided. The methods comprise combination therapy with interleukin-2 (IL-2) or biologically active variant thereof and at least one antagonist anti-CD40 antibody or antigen-binding fragment thereof. In some embodiments, these two therapeutic agents are concurrently administered as two separate pharmaceutical compositions, one containing IL-2 or biologically active variant thereof, which is administered according to a constant IL-2 dosing regimen or a two-level IL-2 dosing regimen, the other containing the antagonist anti-CD40 antibody or suitable antigen~ binding fragment thereof, which is administered according to a weekly dosing regimen, or alternatively is dosed once every two, three, or four weeks. Administering of these two agents together potentiates their effectiveness in promoting a positive therapeutic response. The methods find use in treating CD40-expressing cancers, including B-cell related cancers and solid tumors.

La présente invention a trait à des procédés de traitement d'un sujet pour un cancer comportant des cellules néoplasiques exprimant l'antigène de surface cellulaire CD40. Les procédés comprennent la thérapie de combinaison avec l'interleukine 2 (IL-2) ou un variant biologiquement actif de celle-ci et au moins un anticorps antagoniste anti-CD40 ou un fragment de liaison à l'antigène de celui-ci. Dans certains modes de réalisation, ces deux agents thérapeutiques sont administrés simultanément sous forme de deux compositions pharmaceutiques distinctes, l'une contenant l'IL-2 ou un variant biologiquement actif de celle-ci, qui est administrée selon un schéma posologique constant d'IL-2 ou selon un schéma posologique à deux niveaux d'IL-2, l'autre contenant l'anticorps antagoniste anti-CD40 ou un fragment approprié de liaison à l'antigène de celui-ci, qui est administré selon un schéma posologique hebdomadaire, ou en variante selon un dosage d'une fois toutes les deux, trois, ou quatre semaines. L'administration de ces deux agents conjointement potentialise leur efficacité dans la promotion d'une réponse thérapeutique positive. Les procédés sont applicables dans le traitement de cancers exprimant le CD40, y compris des cancers liés à la cellule B et des tumeurs solides.

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