Abstract: The invention relates to a modified antibody which contains two or more H chain V regions and two or more L chain V regions of monoclonal antibody and can transduce a signal into cells by crosslinking TPO receptor to thereby exert TPO agonist action. The modified antibody can be used as a TPO signal transduction agonist and, therefore, useful as a remedy for various diseases such as platelet-reduction-related blood diseases, thrombopenia following chemotherapy for cancer or leukemia, etc.

Abstract: The invention relates to a modified antibody which contains two or more H chain V regions and two or more L chain V regions of monoclonal antibody and can transduce a signal into cells by crosslinking TPO receptor to thereby exert TPO agonist action. The modified antibody can be used as a TPO signal transduction agonist and, therefore, useful as a remedy for various diseases such as platelet-reduction-related blood diseases, thrombopenia following chemotherapy for cancer or leukemia, etc.

Abstract: The invention relates to a modified antibody which contains two or more H chain V regions and two or more L chain V regions of monoclonal antibody and can transduce a signal into cells by crosslinking TPO receptor to thereby exert TPO agonist action. The modified antibody can be used as a TPO signal transduction agonist and, therefore, useful as a remedy for various diseases such as platelet-reduction-related blood diseases, thrombopenia following chemotherapy for cancer or leukemia, etc.

Abstract: Anti-human Mpl antibodies were isolated and purified. Anti-human Mpl diabodies and anti-human Mpl sc(Fv)2 were prepared using genetic engineering techniques and anti-human Mpl sc(Fv)2 was also humanized. The diabodies and sc(Fv)2 were assayed for TPO-like agonistic activity, and were found to have activities higher than those of anti-human Mpl antibodies, or activities equivalent to or higher than those of naturally-occurring human TPO ligand.

Abstract: Anti-human Mpl antibodies were isolated and purified. Anti-human Mpl diabodies and anti-human Mpl sc(Fv)2 were prepared using genetic engineering techniques and anti-human Mpl sc(Fv)2 was also humanized. The diabodies and sc(Fv)2 were assayed for TPO-like agonistic activity, and were found to have activities higher than those of anti-human Mpl antibodies, or activities equivalent to or higher than those of naturally-occurring human TPO ligand.

Abstract: Anti-human Mpl antibodies were isolated and purified, and then anti-human Mpl diabodies and anti-human Mpl sc(Fv)2 were purified using genetic engineering techniques. Furthermore, the present inventors succeeded in humanizing anti-human Mpl sc(Fv)2. The diabodies and sc(Fv)2 were assayed for TPO-like agonistic activity, and were found to have activities higher than those of anti-human Mpl antibodies, or activities equivalent to or higher than those of naturally-occurring human TPO ligand.

Abstract: The present invention provides tandem diabodies and triabodies against TRAIL receptors, wherein the tandem diabodies and triabodies exhibit greater cytotoxicity as single molecules than whole IgG antibodies. The present invention demonstrates that antibodies that enhance polymerization are useful when aiming to induce cell apoptosis via receptors such as TRAIL receptors, which require polymerization of receptor molecules on the surface of cell membranes to transduce cell death signals.

Abstract: By analyzing the mechanism for inducing a histone deacetylase inhibitor (Trichostatin A)-mediated expression of cyclin-CDK inhibitory factor having a proliferation suppressing effect (tumor-suppressing effect), it was revealed that the binding of Sp3 to the Sp1 binding sequence within a promoter is important in the expression of the above factor. Thus, a novel antitumor agent can be developed by screening a pharmaceutical agent capable of elevating Sp3 activity.

Abstract: Anti-human Mpl antibodies were prepared, and from these three types of antibodies with strong binding activity were selected. An expression system for single-chain antibodies derived from these selected antibodies was constructed using genetic engineering techniques. The anti-human Mpl antibodies and anti-human Mpl single-chain antibodies were assessed for TPO-like agonist activity using BaF3-human Mpl that proliferates TPO-dependently. It was found that while the anti-human Mpl antibodies did not exhibit agonistic activity, the anti-human Mpl single-chain antibodies showed agonistic activity. This shows that when screening for modified antibodies with agonistic activity, it is beneficial to determine agonistic activity after modifying antibodies with antigen-binding activity.

Abstract: Anti-human Mpl antibodies were isolated and purified, and then anti-human Mpl diabodies and anti-human Mpl sc(Fv)2 were purified using genetic engineering techniques. Furthermore, the present inventors succeeded in humanizing anti-human Mpl sc(Fv)2. The diabodies and sc(Fv)2 were assayed for TPO-like agonistic activity, and were found to have activities higher than those of anti-human Mpl antibodies, or activities equivalent to or higher than those of naturally-occurring human TPO ligand.

Abstract: The invention relates to a modified antibody which contains two or more H chain V regions and two or more L chain V regions of monoclonal antibody and can transduce a signal into cells by crosslinking TPO receptor to thereby exert TPO agonist action. The modified antibody can be used as a TPO signal transduction agonist and, therefore, useful as a preventive and/or remedy for various diseases such as platelet-reduction-related blood diseases, thrombopenia following chemotherapy for cancer or leukemia, etc.