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Induction and increase of HLA-DR antigen expression by immune interferon on ML-3 cell line enhances the anti-HLA-DR immunotoxin activity.

Abstract：

:In order to evaluate the impact of induction and increase target antigen expression on immunotoxin potency, we measured the potentiating effect of recombinant immune interferon-gamma (rIFN-gamma) on the cytotoxicity of an anti HLA-DR ricin A-chain immunotoxin (2G5 RTA-IT) on the myeloid cell line ML-3. After 48 h of incubation with rIFN-gamma (500 U/ml) the percentage of 2G5-positive cells increased from 40% to 79%, and the 2G5 mean density was enhanced by 10-fold (11,000 versus 110,000 molecules/cell). Concurrently, rIFN-gamma pretreatment induced a dramatic improvement of 2G5 RTA-IT dose-effect cytotoxicity, as well as immunotoxin cytotoxicity kinetics. When 2G5 RTA-IT was used at the optimal dose of 10(-8)M (the maximum dose which avoided non-specific ricin A-chain cytotoxicity), the immunotoxin-induced cell kill increased with the percentage of DR-positive ML-3 cells according to a similar linear-logarithmic function of rIFN-gamma concentration. Moreover, in the same range of rIFN-gamma concentrations, the killing values and the percentage of DR-positive ML-3 cells were similar if not identical. These findings imply that the enhancement of 2G5 RTA-IT cytotoxicity by rIFN-gamma is mainly related to the rIFN-gamma 2G5 antigen induction on HLA-DR negative cells when immunotoxin was used at 10(-8) M. Furthermore, 2G5 RTA-IT dose-effect cytotoxicity on DR-expressing ML-3 cells, when used at lower concentrations, was also increased by rIFN-gamma in a dose-dependent manner. This result suggests that for immunotoxin concentrations close to the limiting membrane saturation dose (10(-10)M), rIFN-gamma may not solely act by inducing HLA-DR expression on DR-negative ML-3 subpopulation but also by increasing individual cellular DR density on DR expressing ML-3 cells. Finally, our study showed that immunotoxin potency on malignant cell populations which display an heterogeneous antigen expression, could be greatly improved by the use of rIFN-gamma.

journal_name

Clin Exp Immunol

journal_title

Clinical and experimental immunology

authors

Chiron M,Jaffrezou JP,Carayon P,Bordier C,Roubinet F,Xavier C,Brandely M,Laurent G

doi

10.1111/j.1365-2249.1990.tb05429.x

subject

Has Abstract

pub_date

1990-11-01 00:00:00

pages

214-20

issue

eissn

0009-9104

issn

1365-2249

journal_volume

pub_type

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Induction and increase of HLA-DR antigen expression by immune interferon on ML-3 cell line enhances the anti-HLA-DR immunotoxin activity.