Dendritic cells pulsed with a bisphosphonate

Inventors

Nieda, Mie • Isogai, Manami • Kakimi, Kazuhiro

Assignees

Medinet Co Ltd

Abstract

The present invention provides dendritic cells capable of efficiently activating and/or proliferating γδ T-cells in vivo and/or in vitro, pharmaceutical compositions comprising said dendritic cells, therapeutic methods and γδ T-cell culture methods utilizing said dendritic cells. By pulsing immature dendritic cells derived from peripheral blood monocytes with a bisphosphonate-based bone metabolism improving drug to enable the cells to activate γδ T-cells, and cultivating them with a cell subset containing γδ T-cells, γδ T-cells can be activated and/or proliferated. This allows for easy proliferation of γδ T-cells without burdening a patient, leading to practical applications of immune cell therapies that utilize γδ T-cells.

Core Innovation

The invention relates to cultured, isolated dendritic cells that are in vitro pulsed with a bisphosphonate-based bone metabolism improving drug. The pulsed dendritic cells have enhanced functional activity for activating and/or proliferating γδ T-cells in culture compared with cultured, isolated dendritic cells that have not been exposed to a bisphosphonate-based bone metabolism improving drug.

The bisphosphonate-based bone metabolism improving drugs include pamidronic acid, alendronic acid, zoledronic acid, risedronic acid, ibandronic acid, incadronic acid, etidronic acid, and salts and hydrates thereof. The dendritic cells can be immature dendritic cells, or a mixture of immature and mature dendritic cells, with an enhanced effect described for immature dendritic cells.

The document further describes pharmaceutical compositions that include the cultured, isolated dendritic cells pulsed in vitro with a bisphosphonate-based bone metabolism improving drug, where the pulsed dendritic cells have enhanced functional activity for activating and/or proliferating γδ T-cells in culture compared with dendritic cells not exposed to the bisphosphonate-based bone metabolism improving drug.

Claims Coverage

The partial content provides two independent claims. They collectively cover cultured, isolated dendritic cells pulsed in vitro with a bisphosphonate-based bone metabolism improving drug and a pharmaceutical composition comprising such pulsed dendritic cells, both having enhanced functional activity for activating and/or proliferating γδ T-cells in culture. Across the independent claims, three main inventive elements appear: in vitro pulsing with a bisphosphonate-based bone metabolism improving drug, enhanced γδ T-cell activation or proliferation relative to non-exposed dendritic cells, and cultured, isolated dendritic cell material.

Overall claim coverage focuses on bisphosphonate-pulsed cultured, isolated dendritic cells, alone and within a pharmaceutical composition, that exhibit enhanced functional activity for activating and/or proliferating γδ T-cells in culture compared with dendritic cells not exposed to the bisphosphonate-based bone metabolism improving drug. Dependent claims further specify bisphosphonate selections, dendritic cell maturation state, and an optional washing with a pharmaceutically acceptable isosmotic washing solution.

Stated Advantages

Documented Applications