CHIMERIC TNF LIGANDS
    1.
    发明授权
    CHIMERIC TNF LIGANDS 有权
    CHIMERE TNF配体

    公开(公告)号:EP1465912B9

    公开(公告)日:2009-08-12

    申请号:EP02797229.8

    申请日:2002-12-05

    摘要: The present invention is directed to an isolated polynucleotide sequence encoding a chimeric TNFalpha, comprising a first nucleotide sequence encoding a domain or subdomain of a tumor necrosis factor ligand other than TNFalpha, wherein the encoded domain or subdomain replaces a cleavage site of native TNFalpha, and a second nucleotide sequence encoding a domain or subdomain of native TNFalpha that binds to a TNFalpha receptor. The encoded chimeric TNFalpha is significantly less susceptible to cleavage from the cellular surface and, as a result can increase the concentration of a ligand capable of binding to a TNFalpha receptor on the surface of a cell. The chimeric TNFalpha is therefore useful in methods for inducing apoptosis of a cell expressing a TNFalpha receptor, inducing activation of an immune system cell and treating neoplastic cells, by introducing into the cell of interest an isolated polynucleotide sequence encoding a chimeric TNFalpha that is expressed on the surface of the cell.

    CHIMERIC CD154
    7.
    发明公开
    CHIMERIC CD154 有权
    嵌合配体CD154

    公开(公告)号:EP1509253A1

    公开(公告)日:2005-03-02

    申请号:EP03755453.2

    申请日:2003-05-23

    CPC分类号: C07K14/70575

    摘要: The present invention provides for an isolated polynucleotide sequence encoding a chimeric CD154, comprising a first nucleotide sequence encoding an extracellular subdomain of non-human CD154, preferably murine CD154, that replaces a cleavage site of human CD154, and a second nucleotide sequence encoding an extracellular subdomain of human CD154 that binds to a human CD154 receptor. The first nucleotide sequence preferably further encodes an extracellular subdomain of non­human CD154 that is critical for expression of said CD154 by cells, such as human CD40+ cells, and another extracellular domain that detects expression of the chimeric CD154 by binding to anti-murine antibodies. The second nucleotide sequence preferably further encodes an extracellular subdomain of human CD154 to which functionally inhibitory anti-CD154 antibodies bind. The present invention also provides for the chimeric CD154 that is encoded by the above-described polynucleotide sequence, an expression vector and a genetic vector comprising the polynucleotide sequence, a host cell comprising the expression vector or the genetic vector, a process for producing the chimeric CD154, and methods for utilizing the expression vectors and genetic constructs containing the chimeric CD154 polynucleotide sequences.