Process for production of natural killer cells
View Patent ↗A process for producing a cell mass containing natural killer cells, characterized by involving a step of carrying out the expansion culture of a cell mass containing natural killer cells and/or cells capable of being differentiated into natural killer cells in the presence of a biological response modifier and cells that has been so treated as to lose a proliferation capability, and others.
1. A process for preparing a cell population containing a natural killer cell, comprising,
providing a first cell population containing a T cell that has been expansion-cultured in the presence of an anti-CD3 antibody, or an anti-CD3 antibody and a polypeptide having an amino acid sequence derived from fibronection, and then subjected to a treatment which diminishes its proliferation ability,
expansion-culturing a second cell population containing a natural killer cell and/or a cell capable of differentiating into a natural killer cell, in the presence of the first cell population and a preparation derived from Streptcoccus pyogenes or Bacillus Calmette Guerin (BCG) or a preparation derived from BCG cell wall.
2. The process according to claim 1 , wherein the preparation is a preparation derived from Streptococcus pyogenes and is OK-432.
3. The process according to claim 1 , wherein the T cell was derived from the same individual as that of the natural killer cell or the cell capable of differentiating into a natural killer cell.
4. The process according to claim 1 , wherein the expansion-culturing comprises adding the first cell population a plural number of times.
5. The process according to claim 1 , wherein a peripheral blood mononuclear cell is used as the natural killer cell and/or the cell capable of differentiating into a natural killer cell.
6. A process for preparing a cell population containing a natural killer cell, comprising the steps of:
(i) expansion-culturing a cell population containing a T cell or a precursor T cell in the presence of an anti-CD3 antibody, or an anti-CD3 antibody and a polypeptide having an amino acid sequence derived from fibronection to prepare an expansion-cultured T cell population, and diminishing proliferation ability of the expansion-cultured T cell population, and
(ii) expansion-culturing a cell population containing a natural killer cell and/or a cell capable of differentiating into a natural killer cell, in the presence of a preparation derived from Streptcoccus pyogenes or Bacillus Calmette Guerin (BCG) or a preparation derived from BCG cell wall, and the expansion-cultured T cell population of which the proliferation ability has been diminished obtained by step (i).
7. A process for preparing a cell population containing a natural killer cell, comprising a step of expansion-culturing a cell population containing a natural killer cell and/or a cell capable of differentiating into a natural killer cell, in the presence of a bioresponse modifying agent and a T-cell which has been subjected to a treatment which diminishes its proliferation ability,
wherein the bioresponse modifying agent is a bacterium-derived preparation, and wherein the T-cell which has been subjected to a treatment which diminishes its proliferation ability is an expansion-cultured T-cell population which has been subjected to a treatment which diminishes it proliferation ability, and
wherein the proportion of natural killer cells after 21 days of expansion culturing is increased by at least 333-fold.