In vitro generation of lymphocytotoxicity to autochthonous leukaemic cells in chronic myeloid leukaemia

Abstract

Summary.-Lymphocytes from 13 chronic myeloid leukaemia (CML) patients in remission were tested for their ability to differentiate in vitro into a cell population cytotoxic to autochthonous target leukaemic cells. CML remission lymphocytes were cultured in vitro with autochthonous leukaemic cells and allogeneic normal lymphocytes from an unrelated donor, singly or in combination. The cytotoxic lymphocytes obtained after 7 days of culture were tested for their ability to kill autochthonous leukaemic cells in a 3h 5lCr-release assay. It was found that with the allogeneic stimulus alone, cytotoxicity was generated in 5/13 cases, whilst stimulation of lymphocytes with autochthonous leukaemic cells alone induced cytotoxicity in 7/13 cases. In contrast, anti-leukaemic cytotoxicity was shown in 12/13 cases when responder lymphocytes were stimulated with both autochthonous leukaemic and unrelated allogeneic normal lymphocytes.The specificity of cytotoxicity was confirmed using other targets such as autochthonous PHA-transformed lymphoblasts and mouse L1210 cells. In 1/5 cases, CML remission lymphocytes stimulated with autochthonous leukaemic cells showed cytotoxicity to PHA-transformed autochthonous normal lymphoblasts, whilst 1/4 patients showed nonspecific cytotoxicity to L1210 cells when lymphocytes were cultured in MLC or MLTC, as well as in a 3-cell assay.

Treatment of fresh human leukaemia cells with actinomycin D enhances their lysability by natural killer cells

“…For the Vg target ( Figure IA) IFN treatment of effector cells alone resulted in a The doses found suitable for enhancement of NK cell-mediated lysis of fresh human leukaemia cells were lower than the ActD concentrations of 40 pg ml-1 used by Schlager et al (1979) for enhanced complement-dependent lysis of a guinea pig hepatoma, but they are comparable to the lugml-l dose used by Kunkel et al (1981) for the enhancement of NK cell-mediated lysis of murine fibroblasts.…”

“…Treatment of the fibroblasts with cycloheximide or Actinomycin D, however, induces strong NK cell mediated lysis. (Collins et al, 1981;Kunkel & Welsh, 1981). In vitro derived carcinogen-transformed fibroblasts were highly NK sensitive, but again became resistant when passaged in mice with high NK cell activity (Collins et al, 1981).…”

“…Recent studies with various drugs including cytostatics (Schlager & Ohanian, 1979;Schlager, 1982;Collins, 1981;Kunkel & Welsh, 1981) demonstrated that treatment of the tumour targets can modulate their susceptibility to lysis.…”

“…Attempts to enhance cell-mediated lysis of human leukaemia cells initially focused on the effector cells, using in vitro stimulation techniques with irradiated leukaemia cells, allogeneic cells or interferon (IFN) (Khare et al, 1980;Moore et al, 1982;Lee & Oliver, 1978;Pattengale et al, 1982;Taylor, 1981;Zarling et al, 1976;1978;. Recent studies with various drugs including cytostatics (Schlager & Ohanian, 1979;Schlager, 1982;Collins, 1981;Kunkel & Welsh, 1981) demonstrated that treatment of the tumour targets can modulate their susceptibility to lysis.…”

Concanavalin A induced suppressor cell activity and autorosette forming cells in chronic myeloid leukemia patients

“…In our earlier studies we demonstrated that lymphocytes from chronic myeloid leukaemia (CML) patients in remission react to leukaemiaassociated antogens in vitro (Gangal et al, 1976(Gangal et al, , 1979Khare et al, 1981). When a small group of patients was followed up through 2nd and 3rd cycles of relapse and remission, it was observed that leukaemia associated in vitro immune reactivity was negatively correlated with the progress of the disease (Gangal et al, 1977).…”