Mouse tumors are heterogeneous in their susceptibility to syngeneic lymphokine-activated killer cells and delineate functional subsets in such effectors

Self Cite

The efficacy of the association of recombinant interleukin-2 (rIL-2) with chemotherapy has been investigated on an experimental model representative of clinical tumours, i.e. on post-surgical spontaneous metastases of a non-immunogenic tumour. We used the M5076 ovarian reticulum cell sarcoma, which metastasizes to the liver after intra-footpad implantation. Such a tumour appeared to be non-immunogenic by a variety of commonly used in vivo assays. Four clinically widely employed drugs, i.e. doxorubicin, cis-diamminedichloroplatinum II, cyclophosphamide and 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), were tested and BCNU proved to be the most effective one when administered as single injection at the maximum tolerated dose (33 mg/kg i.p.) 1 day after tumour excision. When moderate doses of rIL-2 (6 x 10(5) IU in three injections per day for 5 days) were administered at three different intervals after BCNU, namely before the nadir of white blood cells (1 day after BCNU), at the nadir (3 days after BCNU) or at recovery (6 days after BCNU), no increase in BCNU antitumour activity was observed. The same results were obtained by administering rIL-2 for 5 days before BCNU. Higher doses of rIL-2 (1.2 x 10(6) IU in three injections per day for 5 days), which were always well tolerated in sham-excised non-tumour-bearing mice, proved lethal in two out of four experiments in tumour-bearing animals. In the two experiments in which no lethality was observed, the administration of high doses of rIL-2 1 or 6 days after BCNU significantly increased the antitumour activity of BCNU alone. rIL-2 alone was not active even when administered at high doses. These results indicate that high but not moderate doses of rIL-2 may increase the activity of BCNU against a non-immunogenic tumour. Moreover, they suggest that rIL-2 tolerability is reduced in tumour-bearing mice.

Section: Discussioncontrasting

confidence: 46%

Postsurgical adjuvant chemoimmunotherapy with recombinant interleukin-2 and 1,3-bis-(2-chloroethyl)-1-nitrosurea on spontaneous metastases of a non-immunogenic murine tumour

Acerbis

Cleris

Rodolfo

et al. 1992

Self Cite

“…It is possible that LAK cells derived from NK cells use different target recognition structures from LAK cells derived from T cells. The hypothesis is supported by Sensi et al [15], who have shown that separate LAK effectors with different target cell recognition structures appear in IL-2-stimulated cultures with different time kinetics. It was observed by the same authors that the tumour cells are heterogeneous in their susceptibility to different LAK subpopulations.…”

Section: Discussionmentioning

confidence: 83%

Effect of interferon γ on the sensitivity of bovine-papilloma-virus(BPV1)-transformed cell lines to cell-mediated cytotoxicity

Laatikainen

Schultz-Suhonen

Mäntyjärvi

1992

The effect of interferon gamma (IFN gamma) on the immunogenicity and immunosensitivity of mouse cell lines transformed by bovine papillomavirus type 1 (BPV1) DNA was examined in a syngeneic mouse model. The overnight incubation of BPV1-transformed cell lines with 100 IU/ml IFN gamma did not affect their ability to induce the generation of cytotoxic effector cells but it clearly increased their sensitivity to lysis by interleukin-2-induced lymphokine-activated killer (LAK) cells and by non-specific LAK-type effector cells induced by BPV-1-transformed cell lines. The treatment of two allogeneic lymphoid tumour cell lines, P815X2 and YAC-1, with IFN gamma either decreased or had no effect on their sensitivity to LAK-cell-mediated lysis.

“…Effectors are also generally classified as bearing either NK or T-cell surface markers, the latter having a greater lytic ability towards modified self cells, whereas NK-like LAK cells have superior lytic activity against culmred mmour lines [2,3,9]. Further, the kinetics of LAK growth have been examined and the expansion of LAK effectors with T-celllike phenotypes has been shown to increase with increasing culture periods, there being relatively few T-cell-like LAK cells at 3 days and a significant increase in their number by 7 days [1, 3,9,19]. It should be noted that these studies were performed using a standard medium supplemented with fetal calf serum; however, the LAK cells grown in AIM-V in the experiments reported here killed modified self targets poorly regardless of culture period.…”

Section: Methodsmentioning

confidence: 99%

Effect of culture media on lymphokine-activated killer effector phenotype and lytic capacity

Finkelstein

Miller

1991

We compared the ability of murine lymphokine-activated killer (LAK) cells grown in either a serum-supplemented "standard" medium (alpha MEM plus fetal calf serum) or a serum-free medium (AIM-V) to lyse a range of tumour targets. LAK cells grown in either of the media killed a cultured murine tumour line (YAC-1 lymphoma) well and spared syngeneic "self" cells (concanavalin-A-stimulated splenocytes). However, a striking difference was noted in the ability of LAK cells grown in alpha MEM plus fetal calf serum (as opposed to AIM-V) to kill "modified self" cells (trinitrophenol-modified concanavalin A blasts); LAK cells grown in the former always killed modified self cells better than those grown in the latter. This pattern held under a broad range of experimental manipulations and was found to be related to a relative increase in CD3-bearing LAK cells grown in the standard medium. These data suggest that the two media cannot be used interchangeably. This conclusion may have clinical implications for the use of LAK cells, as animal studies have been done using LAK cells generated in serum-containing medium and clinical studies have used LAK cells generated in serum-free medium.