Methods for inducing a natural killer (nk) cell-mediated...

A - Human Necessities – 61 – K

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A61K 35/14 (2006.01) A61K 38/19 (2006.01) A61K 38/57 (2006.01) A61P 35/00 (2006.01) G01N 33/50 (2006.01) G01N 33/569 (2006.01)

Patent

CA 2682661

The present invention relates to the discovery of novel methods of inducing a natural killer (NK) cell-mediated immune response and increasing NK activity in a mammal for the treatment of tumors and virus infections. The method comprises the steps of isolating peripheral blood mononuclear cells (PBMCs) from the subject, exposing the PBMCs in vitro to protein conjugate comprising granulocyte macrophage colony stimulating factor (GM-CSF) covalently linked to a soluble peptide antigen, under conditions effective to activate the PBMCs, and administering the activated PBMCs to the subject. The invention also relates to a method of detecting in a subject a cytotoxic NK cell-meditated immune response or NK cell activity in vitro by CD336 expression and/or lysis of the K562 tumor line. The invention further relates to a method for determining whether a subject has had a therapeutically effective response to a protein conjugate by assessing the NK activity of activated PBMCs from the subject.

La présente invention concerne la découverte de nouveaux procédés d'induction d'une réponse immunitaire médiée par des cellules tueuses naturelles (NK) et d'augmentation de l'activité des cellules NK chez un mammifère pour le traitement de tumeurs et d'infections virales. Le procédé comprend les étapes consistant à isoler des cellules mononucléaires sanguines périphériques (PBMC) du sujet, exposer les PBMC, in vitro, à un conjugué de protéine comprenant le facteur stimulant les colonies de macrophages et de granulocytes (GM-CSF) lié de manière covalente à un antigène peptidique soluble, dans des conditions efficaces pour activer les PBMC, et administrer les PBMC activées au sujet. L'invention concerne en outre un procédé de détection chez un sujet d'une réponse immunitaire médiée par des cellules NK cytotoxiques ou d'une activité des cellules NK, in vitro, par l'expression de CD336 et/ou la lyse de la lignée tumorale K562. L'invention concerne en outre un procédé pour déterminer si un sujet a eu une réponse thérapeutiquement efficace vis-à-vis d'un conjugué de protéine en évaluant l'activité des cellules NK des PBMC activées du sujet.

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