Expansion of Natural Killer and NTK-Like Cells for Killing CLL Cells

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Leukemia. 2003 Oct;17(10):1973-80.

Expansion of natural killer (NK) and natural killer-like T (NKT)-cell

populations derived from patients with B-chronic lymphocytic leukemia

(B-CLL): a potential source for cellular immunotherapy.

Guven H, Gilljam M, Chambers BJ, Ljunggren HG, Christensson B, Kimby

E, Dilber MS.

1Department of Medicine, Division of Hematology, Karolinska

Institutet, Huddinge University Hospital, Stockholm, Sweden.

B-cell chronic lymphocytic leukemia (B-CLL) is the most common

leukemia in the Western world. It is currently an incurable disease,

making new treatment options such as immunotherapy desirable.

Monoclonal antibodies (Mabs) to surface antigens of the tumor cell is

one option. Administration of cytotoxic cells such as natural killer

(NK) and natural killer-like T (NKT) cells expanded in vitro might be

a useful treatment modality alone or in combination with MAbs.

A limiting step in the development of successful cellular

immunotherapy has been the availability of appropriate cytotoxic

cells. Here, we report the feasibility of expanding populations of

the human killer cells, CD3-CD56+ NK and CD3+CD56+ NKT cells, from

peripheral blood mononuclear cells (PBMCs) of B-CLL patients. The

influence of tumor B cells on the in vitro expansion of killer cells

was assessed by depleting B cells from PBMCs by microbead separation

before culture.

The 21-day cultures from both B-cell- and non-B-cell-depleted PBMC

showed a marked expansion of NK cells, and also of T cells, among

which almost half had the NKT phenotype. Depletion of B cells before

culture did not change the expansion rates of NK and NKT cells

significantly.

In patients with progressive B-CLL, NK cell expansion capacity was

improved after fludarabine treatment when compared to samples

obtained before treatment. Repeated samples of PBMCs from individual

untreated patients with both indolent and progressive disease

cultured under identical conditions gave similar NK cell expansion

rates. Expanded killer cell populations had cytotoxic function

against the NK-sensitive target K562 cell line and expressed high

levels of Granzyme B.

From our studies, we conclude that NK cells as well as NKT cells from

the peripheral blood of B-CLL patients can be expanded, and that

these cells have cytotoxic capacity.

Leukemia (2003) 17, 1973-1980. doi:10.1038/sj.leu.2403083

PMID: 14513047 [PubMed - in process]