Method for the simultaneous induction of CTL and γδT cell

Inventors

Nieda, Mie • Tomiyama, Mai • Muto, Masato

Assignees

Medinet Co Ltd

Abstract

Disclosed are: a method for culture of disease antigen specific CTLs and γδT cells in one culture step conveniently and efficiently; and a pharmaceutical agent and a therapeutic/prophylactic method both of which use a cell produced by the method. Blood is collected and peripheral blood mononuclear cells are separated from the blood. Aminobisphosphonate and a disease antigen are added to the peripheral blood mononuclear cells at the beginning of culture, and the cell culture is carried out for a predetermined period to proliferate/induce disease antigen specific CTLs and γδT cells simultaneously until the numbers of the cells reach values that are effective for the treatment of a disease. The CTLs and the γδT cells thus produced are used for the treatment.

Core Innovation

The invention relates to a one-step method for simultaneous proliferation of disease antigen specific cytotoxic T lymphocytes (CTLs) and γδT cells. The method consists of adding a disease antigen and an aminobisphosphonate to isolated peripheral blood, and culturing the resultant combination in a culture media.

The method is also described for an isolated mononuclear cell fraction of peripheral blood. In certain embodiments, the culture media includes serum and/or plasma and added interleukin-2 (IL-2).

The disease antigen is described as a cancer antigen in at least some embodiments. The aminobisphosphonate includes pamidronic acid, alendronic acid, zoledronic acid, risedronic acid, ibandronic acid, incadronic acid, and salts and/or hydrates of aminobisphosphonates.

Claims Coverage

The document provides four independent claims directed to the simultaneous proliferation of disease antigen specific CTLs and γδT cells. Across these claims, the inventive features include adding a disease antigen together with an aminobisphosphonate to isolated peripheral blood or an isolated mononuclear cell fraction and culturing the combination in a culture media, with emphasis on performing the culturing without a separate in vitro induction step of monocyte-derived dendritic cells from mononuclear cells. Additional independent-claim features specify the disease antigen as a cancer antigen and define culture media components such as serum/plasma and added IL-2.

All independent claims cover culturing peripheral blood or an isolated mononuclear cell fraction with a disease antigen and an aminobisphosphonate to simultaneously proliferate disease antigen specific CTLs and γδT cells. A key distinguishing feature in multiple independent claims is the absence of a separate in vitro induction step for monocyte-derived dendritic cells.

Stated Advantages

Documented Applications