Treatment of b cell diseases using anti-germline antibody...

A - Human Necessities – 61 – K

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A61K 39/395 (2006.01) C07K 16/42 (2006.01) G01N 33/53 (2006.01)

Patent

CA 2623016

Methods for reducing the number of pathologic antibody producing B cells in a patient suffering from an autoimmune disease by administration of an anti- germline antibody are described. Methods for removing pathologic antibodies and B cells and plasma cells producing pathologic antibodies from the body of a patient suffering from autoimmune disease are provided, comprising contacting the blood or plasma of the patient with an immunoadsorbent having specific binding for an epitope present on germline antibodies, particularly VH4-34 antibodies, wherein said contacting results in the reduction in the amount of germline antibodies present in the blood or bone marrow or lymphoid tissue of the patient or the amount of germline antibody producing B cells present in the blood, lymphoid tissues or bone marrow of the patient. Methods for treating a patient suffering from a B cell cancer expressing cell surface germline antibodies by similar methods are also provided. Methods for ex vivo purging bone marrow of pathologic antibody producing B-cells and cancerous B- cells expressing germline antibodies are provided. Methods for monitoring the efficacy of a therapeutic treatment in a patient suffering from an autoimmune disease or B cell cancer are also provided. Kits and uses in preparation of a medicament are also described.

La présente invention concerne des procédés permettant de réduire le nombre de lymphocytes B producteurs d'anticorps pathologiques chez un patient souffrant d'une affection auto-immune par administration d'un anticorps antigerminaux. L'invention concerne également, dans le cas de patients souffrant de maladie auto-immune, des procédés permettant d'éliminer de leurs corps les anticorps et lymphocytes B pathologiques, ainsi que les cellules plasmatiques productrice d'anticorps pathologiques. A cet effet, on met le sang ou le plasma du patient en contact avec un immunoadsorbant comportant une liaison spécifique pour un épitope présent sur les anticorps germinaux, plus particulièrement les anticorps VH4-34. Une telle mise en contact aboutit à une réduction de la quantité de lymphocytes B producteurs d'anticorps germinaux, que ces lymphocytes soient présent dans le sang, les tissus lymphoïdes ou la moelle osseuse. L'invention concerne également un procédé permettant de traiter d'une façon similaire un patient souffrant d'un cancer des lymphocytes B exprimant des anticorps germinaux à la surface des cellules. L'invention concerne également des procédés permettant de purger ex vivo la moelle osseuse des lymphocytes B producteurs d'anticorps pathologiques et des lymphocytes B cancéreux exprimant des anticorps germinaux. L'invention concerne également des procédés permettant de surveiller l'efficacité d'un traitement thérapeutique chez un patient souffrant d'une maladie auto-immune ou de cancer des lymphocytes B. L'invention concerne enfin des nécessaires et leurs utilisations pour l'élaboration d'un médicament.

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