Granulysin, method of obtaining it and uses

Inventors

Luis A. Anel Bernal; Raquel Ibañez Perez; Patricia Guerrero Ochoa; Luis Martinez Lostao; Blanca Conde Guerri; Ramón Hurtado Guerrero; Ana Laura Sanz Alcober; Rocio Navarro Ortiz.

Universidad de Zaragoza; Fundación Agencia Aragonesa para la Investigación y el Desarrollo (ARAID); Fundación para la Investigación Biomédica del Hospital Universitario Puerta del Hierro (FIBHUPHM).

Background

Granulysin (GRNLY) is a protein found in the granules of activated cytotoxic T lymphocytes (CTLs) and human natural killer (NK) cells. When GRNLY is released, high concentrations (in the micromolar range) appear in the immediate area, and its 9 kDa isoform could exert cytotoxicity. The 9 kDa GRNLY shows cytolytic activity against a wide variety of microbes, and its recombinant 9 kDa form is also cytotoxic against tumour cells. Despite the known benefits associated with the selective elimination of malignant cells, numerous practical problems limit the therapeutic use of the conjugates, including inefficient cellular uptake, low cytotoxicity and toxic effects at sites other than the tumour site.

La invención

The present invention relates to the polypeptide granulisina (GRNLY) for use as a systemic medicine, and to a chimeric molecule comprising a recombinant antibody directed against a tumour antigen and the polypeptide (GRNLY) . The results obtained suggest that a GRNLY chimera is a good strategy for achieving its systemic administration, whereby GRNLY reaches the tumour site at concentrations high enough to exert its cytotoxic activity, especially when this chimera forms part of a single polypeptide chain and has been produced in the yeast P. pastoris.