Expanded NK cells
The present invention relates to expanded NK cells. The NK cells have been expanded ex vivo, are activated and have a cytotoxic phenotype. The cytotoxicity against malignant cells is markedly increased compared to non-expanded NK cells. The invention also relates to a method of treatment.
1. A method of treating multiple myeloma by administering to a patient, a composition comprising natural killer (NK) cells produced by:
(a) isolating NK cells from peripheral blood or bone marrow of a patient suffering from multiple myeloma, and
(b) expanding the isolated NK cells ex vivo in the presence of autologous mononuclear cells for about 20 days, in a serum-free stem cell growth medium comprising human albumin, human recombinant insulin, L-glutamine and β-mercaptoethanol (CELLGRO SCGM), wherein said medium is supplemented with anti-CD3 antibody, human serum, and IL-2 for about the first 5 days, and wherein said medium is supplemented with IL-2 and human serum for the remainder of the about 20 days, whereby the expanded said NK cells have:
(i) at least about a 100% increased cytotoxicity against multiple myeloma cells of said patient compared to freshly isolated non-expanded NK cells isolated from said patient, and
(ii) an upregulated expression of at least one natural cytotoxic receptor (NCR).
2. The method according to claim 1 , wherein said natural cytotoxic receptor is upregulated by at least about 50% compared to freshly isolated non-expanded NK cells isolated from said patient.
3. The method according to claim 1 , wherein said at least one natural cytotoxic receptor is selected from the group consisting of 2B4, CD8, CD16, CD27, CD226, NKG2D, NKp30, NKp44 and NKp46.
4. The method according to claim 1 , wherein said NK cells exhibit higher degranulation activity compared to freshly isolated non-expanded NK cells isolated from said patient as determined by CD107a expression.
5. The method according to claim 3 , wherein said at least one natural cytotoxic receptor is 2B4.
6. The method according to claim 5 , wherein said NK cells further have an upregulated expression of a second natural cytotoxic receptor compared to freshly isolated non-expanded NK cells isolated from said patient, wherein the second activating receptor is selected from the group consisting of CD8, CD16, CD27, CD226, NKG2D, NKp30, NKp44 and NKp46.