Novel tumor antigen useful in diagnosis and therapy of...

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G01N 33/574 (2006.01) C07K 14/82 (2006.01) C12N 9/64 (2006.01) A61K 38/00 (2006.01) A61K 39/00 (2006.01)

Patent

CA 2415923

Compositions for the diagnosis and therapy of bladder, lung, ovary, and kidney cancer, derived from or based on a normally prostate-specific, androgen- regulated, cell membrane associated an secreted serine protease termed 20P1F12/TMPRSS2 are described. A full length cDNA comprising the entire coding sequence of the 20P1F12/TMPRSS2 gene (also designated 20P1F12-GTC1 herein) is provided (Figure 1). Among the compositions provided are antibodies that bind to 20P1F12/MPRSS2 proteins and polypeptide fragments thereof, including antibodies labeled with a detectable marker or toxin or therapeutic composition. The invention also provides prognostic and diagnostic methods of examining a biological sample for evidence of disregulated cellular growth by comparing the status of 20P1F12/TMPRSS2 in a corresponding normal sample, wherein alterations in the status of 20P1F12/TMPRSS2 in the biological sample are associated with disregulated cellular growth. The invention further provides various therapeutic compositions and strategies for treating bladder, lung, ovary, and kidney cancer, including particularly, 20P1F12/TMPRSS2 antibody therapy methods and compositions, cancer vaccines, and small molecule therapy.

L'invention concerne des compositions pour le diagnostic et le traitement de cancers de la vessie, du poumon, de l'ovaire et du rein, dérivées ou à base de membrane cellulaire normale spécifique de prostate, régulée par des androgènes, associée à une sérine protéase sécrétée appelée 20P1F12/TMPRSS2 ; un ADNc pleine longueur contenant la séquence de codage complète du gène de 20P1F12/TMPRSS2 (également appelé 20P1F12-GTC1) (Figure 1). Les compositions décrites comprennent des anticorps qui se lient à des protéines de 20P1F12/TMPRSS2 et à des fragments polypeptidiques de celles-ci, y compris des anticorps marqués à l'aide d'un marqueur détectable, d'une toxine ou d'une composition thérapeutique. L'invention concerne aussi des procédés pronostiques et diagnostiques d'examen d'échantillon biologique afin de détecter une croissance cellulaire anormale, par comparaison avec l'état de 20P1F12/TMPRSS2 dans un échantillon normal correspondant ; des modifications de l'état de 20P1F12/TMPRSS2 de l'échantillon biologique étant associées à une croissance cellulaire anormale. L'invention concerne en outre diverses compositions et stratégies thérapeutiques pour traiter un cancer de la vessie, du poumon, de l'ovaire et du rein, qui comprennent notamment des procédés et des compositions utilisant un polypeptide de 20P1F12/TMPRSS2 et un anticorps anti-20P1F12/TMPRSS2, des vaccins contre le cancer et un traitement à petites molécules.

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