Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes.

Abstract

Activation in lectin-free interleukin 2 (IL-2) containing supernatants of peripheral blood mononuclear leukocytes (PBL) from cancer patients or normal individuals resulted in expression of cytotoxicity toward 20 of 21 natural killer (NK)-resistant fresh solid tumor cells tested. Fresh solid tumor cells were resistant to NK-mediated lysis in 10 autologous patients' PBL-tumor interactions, and from 17 normal individuals tested against 13 allogeneic fresh tumors. Culture of PBL in IL-2 for 2-3 d was required for the lymphokine activated killers (LAK) to be expressed, and lytic activity toward a variety of NK-resistant fresh and cultured tumor targets developed in parallel. Autologous IL-2 was functional in LAK activation, as well as interferon-depleted IL-2 preparations. Irradiation of responder PBL before culture in IL-2 prevented LAK development. Precursors of LAK were present in PBL depleted of adherent cells and in NK-void thoracic duct lymphocytes, suggesting that the precursor is neither a monocyte nor an NK cell. LAK effectors expressed the serologically defined T cell markers of OKT.3, Leu-1, and 4F2, but did not express the monocyte/NK marker OKM-1. Lysis of autologous fresh solid tumors by LAK from cancer patients' PBL was demonstrated in 85% of the patient-fresh tumor combinations. Our data present evidence that the LAK system is a phenomenon distinct from either NK or CTL systems that probably accounts for a large number of reported nonclassical cytotoxicities. The biological role of LAK cells is not yet known, although it is suggested that these cells may be functional in immune surveillance against human solid tumors.

Gene transfer of human interferon gamma complementary DNA into a renal cell carcinoma line enhances MHC-restricted cytotoxic T lymphocyte recognition but suppresses non-MHC-restricted effector cell activity

“…Both CD3 − and CD3 + LAK cells show non-MHC-restricted specificity. 12,13 While the molecular basis of tumor cell recognition by these effector cell types remains to be defined it has been found that the adhesion molecules ICAM-1 (CD54) and leukocyte-associated function molecule 3 (LFA-3, CD58) are important for optimal effector-target cell interactions. [14][15][16] More rarely, classical MHC-restricted CTL have been identified in RCC patients.…”

High Dose IL‐2‐Activated Murine Natural Killer (A‐NK) Cells Accumulate Glycogen and Granules, Lose Cytotoxicity, and Alter Target Cell Interaction In Vitro

“…It is established that certain lymphocytes cultured in the presence of IL-2 develop into an activated natural killer cell phenotype (lymphokine activated killer cells; LAK cells) with enhanced cytotoxic activity against malignant target cells [1][2][3][4]. There are numerous clinical attempts based on adoptive immunotherapy (AIT) of cancer disease with various subsets of LAK cells [5][6][7][8][9].…”

Lysis of allogeneic and autologous melanoma cells by IL-7-induced lymphokine-activated killer cells

“…Any form of chemotherapy, immunotherapy or hormone therapy had to be discontinued 6 weeks before blood collection. After removal of the adherent monocytes by incubating the PBMCs on plastic plates for 1 h at 37C, the PBLs were decanted and either cryopreserved or immediately processed for the generation of LAK cells (Grimm et al, 1982;Schadendorf et al, 1994b). In short, PBLs were incubated at a density of 2 x 106 cells ml-' in RPMI-1640 supplemented with glutamine, fetal calf serum and antibiotics as mentioned above, and 1,000 U ml1' IL-7 or 100 U ml1' IL-2.…”