Dose definition and activity evaluation study of the tumor-targeting human L19IL2 monoclonal antibody-cytokine fusion protein in combination with Dacarbazine in patients with metastatic melanoma - L19IL2 in combination with Dacarbazine in patients with metastatic melanoma

Start Date17 Jan 2008

Sponsor / Collaborator

Philogen SpA

100 Clinical Results associated with Monoclonal antibody cytokine fusion protein therapeutic (Viela Bio)

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01 Jan 2001·NeuroscienceQ3 · MEDICINE

Functional blocking of integrin-associated protein impairs memory retention and decreases glutamate release from the hippocampus

Q3 · MEDICINE

Article

Author: L.Y Tsai ; H.P. Chang ; E.H.Y. Lee ; Y.L. Ma ; F.P. Lindberg ; F.J. Wan

We have previously demonstrated that integrin-associated protein is involved in memory consolidation of one-way inhibitory avoidance learning in rats and mice. In the present study, we examined the effects of functional blocking of integrin-associated protein on memory retention, long-term potentiation and glutamate release in mice as well as on cell attachment to extracellular matrix protein in primary cultures. The results indicated that integrin-associated protein monoclonal antibody miap301, when directly injected into the dentate gyrus of the hippocampus at moderate doses, significantly impairs memory retention in mice in the same one-way inhibitory avoidance task and decreases the amplitude of tetanic stimulation-induced long-term potentiation in dentate gyrus neurons. At a dose that effectively impairs both memory retention and long-term potentiation, integrin-associated protein monoclonal antibody also significantly blocks potassium chloride-induced glutamate release from the hippocampus in vivo. Results from western blot confirmed the presence of integrin-associated protein at the synaptic area. Cell adhesion experiments further revealed that integrin-associated protein monoclonal antibody markedly inhibits granular cell attachment to thrombospondin, the extracellular matrix protein known to bind integrin-associated protein, but not to collagen and laminin, the extracellular matrix proteins known to bind integrin. From these results we suggest that integrin-associated protein monoclonal antibody may impair synaptic plasticity and behavioral plasticity in mice through blockade of granular cell attachment to extracellular matrix protein and the subsequent signal transduction, and through inhibition of glutamate release from the hippocampus.

100 Deals associated with Monoclonal antibody cytokine fusion protein therapeutic (Viela Bio)

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Indication	Highest Phase	Country/Location	Organization	Date
Inflammation	Preclinical	US	Viela Bio, Inc.	-

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