The Research Foundation of State University of New York
发明人:
M. Kerry O'Banion,Sabine Brouxhon,Stephanos Kyrkanides
申请号:
BR112013010535
公开号:
BR112013010535A2
申请日:
2011.10.27
申请国别(地区):
BR
年份:
2017
代理人:
摘要:
compositions targeting the soluble extracellular domain of e-cadherin and related methods for cancer therapy. The present invention is based, in part, on our finding that targeting epitopes within one or more of the e-cadherin ec2-ec5 subdomains results in the death of epithelium-derived tumor cells, but not in the death of normal epithelial cells. , healthy or non-epithelial cells, including endothelial cells and fibroblasts. Accordingly, the compositions of the invention include polypeptides having an amino acid sequence of one or more of the ec2-ec5 sub-domains of e-cadherin and biologically active variants thereof; expression vectors and cells for expressing such polypeptides; and agents (e.g. antibodies) that target the ec2-ec5 subdomains. The methods of the invention include methods of identifying and producing polypeptides having an amino acid sequence of one or more of the e-cadherin ec2-ec5 subdomains or a biologically active variant thereof; methods of generating agents, such as antibodies, that are intended for these polypeptides, and methods of administering such agents or causing their production in vivo to treat epithelial cancers or reduce the risk of their occurrence or recurrence.composições direcionadas o domínio extracelular solúvel de e-caderina e métodos relacionados para terapia de câncer. a presente invenção é baseada, em parte, na nossa descoberta que ter como alvo epítopos dentro de um ou mais dos subdomínios ec2-ec5 de e-caderina resulta na morte de células de tumor derivadas do epitélio, mas não na morte de células epiteliais normais, saudáveis ou células não-epiteliais, incluindo células endoteliais e fibroblastos. nesse sentido, as composições da invenção incluem polipeptídeos tendo uma sequencia de aminoácido de um ou mais dos subdomínios ec2-ec5 de e-caderina e variantes biologicamente ativos dos mesmos; vetores de expressão e células para expressar tais polipeptídeos; e agentes (por exemplo, anticorpos) que se direcionam aos subdomíni