Anti-idiotypic monoclonal antibody to a T-cell chronic lymphatic leukemia

1989 ◽  
Vol 28 (3) ◽  
Author(s):  
CarlHarald Janson ◽  
MahmoodJeddi Tehrani ◽  
H�kan Mellstedt ◽  
Hans Wigzell
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
Chronic Lymphatic Leukemia ◽  
Lymphatic Leukemia

scholarly journals Blood kinetics, tissue distribution, and radioimaging of anti-common chronic lymphatic leukemia antigen (cCLLa) monoclonal antibody CLL2 in mice transplanted with cCLLa-bearing human leukemia cells

Blood ◽  
1990 ◽  
Vol 75 (9) ◽  
pp. 1853-1861 ◽  
Author(s):  
GB Faguet ◽  
JF Agee ◽  
JT DiPiro
Keyword(s):  
Monoclonal Antibody ◽  
Specific Activity ◽  
Human Leukemia ◽  
Chronic Lymphatic Leukemia ◽  
Prolymphocytic Leukemia ◽  
Normal Tissues ◽  
Lymphatic Leukemia ◽  
Human Leukemia Cells ◽  
Glycoprotein Antigen ◽  
Leukemia Antigen

Abstract The blood kinetics and biodistribution of anti-common chronic lymphatic leukemia antigen (cCLLa) monoclonal antibody (MoAb) CLL2 were assessed in mice bearing cCLLa+ tumors. The cCLLa is a 69-Kd glycoprotein antigen expressed selectively by malignant B cells in human CLL, hairy cell leukemia (HCL), and prolymphocytic leukemia. Immunoreactive 125I- CLL2 (5 micrograms/mouse, specific activity 4.3 microCi/micrograms) was injected intravenously in mice bearing HCL-derived EH xenografts, and blood kinetics and biodistribution were ascertained up to 16 days postinjection. Radioimages were also obtained up to 72 hours after injecting 10 micrograms/mouse (specific activity 50.1 microCi/micrograms) of 125I-CLL2. Distinct 125I-CLL2 blood kinetics were observed in EH engrafted compared with tumor-free mice including: a longer 125I-CLL2 T 1/2 (153 hours v 72 hours), and a considerably greater blood clearance (173 mg/h v 54.7 mg/h) with biexponential rather than monoexponential configuration; and a greater volume of antibody distribution (31,483 mg v 5,729 mg). These data suggest more rapid tissue uptake by grafted tumours. Preferential 125I-CLL2 uptake by EH tumours relative to normal tissues was observed beginning 24 hours postinjection (mean ratio, 4.2) with average peak tumor 125I-CLL2 levels of 428.7 pg/mg. 125I-CLL2 uptake selectivity by EH tumor cells was also supported by: (1) negligible 125I-CLL2 uptake by cCLLa- Molt-4 xenografts (average 29.1 pg/mg 24 hours postinjection); (2) background uptake of cCLLa-irrelevant MoAb 131I-LEU1 by CD5- EH xenografts (average 31.4 pg/mg 48 hours postinjection); and (3) by scintigraphy. The EH xenograft mouse model might be useful to ascertain preclinically the anti-tumor effect of anti-cCLLa MoAbs and of their conjugated derivatives.

scholarly journals Production and regulation of interleukin-2 in human lymphoblastic leukemias studied with T-cell monoclonal antibodies

Blood ◽  
1983 ◽  
Vol 61 (4) ◽  
pp. 781-789 ◽  
Author(s):  
S Venuta ◽  
R Mertelsmann ◽  
K Welte ◽  
SP Feldman ◽  
CY Wang ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Lymphoblastic Leukemia ◽  
Interleukin 2 ◽  
Gel Filtration ◽  
Lymphatic Leukemia ◽  
Daudi Cells ◽  
Self Replication

Abstract Human leukemias are illnesses of hemopoietic stem cells that go through processes of self-replication and partial differentiation under the control of as yet largely unknown growth and differentiation factors. IL-2 is a powerful factor controlling proliferation of normal T cells. We report that acute lymphoblastic leukemias of T and non-B, non-T phenotypes produce a growth factor after mitogen stimulation. This factor is able to support the proliferation of human and murine IL-2- dependent cytotoxic cells, has a mol wt of 26,000 daltons by gel filtration, an isoelectric point of 6.6, and its biologic activity is inhibited by an anti IL-2 monoclonal antibody. This factor is, therefore, by all parameters studied very similar to IL-2 produced by normal lymphocytes. A recently developed monoclonal antibody, Pan T2, binds to normal T cells, renders T cells responsive to IL-2, and induces the release of IL-2, which in turn provides the second signal for T-cell proliferation. Mononuclear cells from acute lymphoblastic leukemia do not respond to the addition of this monoclonal antibody unless cocultured with irradiated Daudi cells. Since normal T cells do not require Daudi to produce IL-2 and since Daudi cells do not produce IL-2 under any conditions, we conclude that the cell responsible for IL- 2 production in acute lymphatic leukemia is a leukemic T cell with an altered mechanism of IL-2 production at the level of the Pan T2 binding site.

Appearance of the T-cell marker CD8 on B chronic lymphatic leukemia cells in long-term cultures

1991 ◽  
Vol 34 (3) ◽  
pp. 181-185 ◽  
Author(s):  
Ruth Farkas ◽  
Shlomo Ben-Efraim ◽  
Yosef Manor ◽  
Israel Zan-Bar ◽  
Abraham Klajman
Keyword(s):  
T Cell ◽  
Leukemia Cells ◽  
Chronic Lymphatic Leukemia ◽  
Cell Marker ◽  
Lymphatic Leukemia ◽  
Lymphatic Leukemia Cells

scholarly journals T Activation in a Patient with T Cell Chronic Lymphatic Leukemia

1986 ◽  
Vol 75 (2) ◽  
pp. 122-122 ◽  
Author(s):  
Naomi A. Levene ◽  
Cyril Levene ◽  
Alex Dvilansky ◽  
Dan Buskila
Keyword(s):  
T Cell ◽  
Chronic Lymphatic Leukemia ◽  
Lymphatic Leukemia

scholarly journals Decrease and altered distribution of human T antigen on chronic lymphatic leukemia cells of T type, suggesting a clonal origin

Blood ◽  
1976 ◽  
Vol 47 (5) ◽  
pp. 723-736 ◽  
Author(s):  
E Thiel ◽  
H Rodt ◽  
D Huhn ◽  
S Thierfelder
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Sheep Erythrocyte ◽  
T Antigen ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Chronic Lymphatic Leukemia ◽  
Lymphatic Leukemia ◽  
Clonal Origin ◽  
Lymphatic Leukemia Cells

Abstract B- and T-cell markers were studied in a patient with chronic lymphocytic leukemia and erythroderma. The absence of immunoglobulin, complement receptor, and Fc receptor, and the presence of sheep erythrocyte receptor and T-cell antigen on the membrane of the leukemic cells classified them as thymus derived. Using quantitative microphotometric immunoautoradiography, surface antigen densities were measured at the cellular level with the following results: (1) The density of T-antigenic sites was less on leukemic cells compared to normal T lymphocytes. (2) The T-antigen densities of leukemic lymphocytes varied less from cell to cell forming a homogeneous peak in histograms. (3) An Ig density of normal B lymphocytes was demonstrated on the residual T-antigen-negative cells. The results were qualitatively confirmed by direct immunofluorescence and electron microscopy with peroxidase-labeled antibodies. Furthermore, the surface antigens were quantitative microcomplement fixation test which revealed reduced binding of anti-T-cell antibodies and complement, and no antiglobulin fixation on the leukemic lymphocytes. Since lymphocytes with normal T-antigen concentration could not be found among the leukemic T lymphocytes, a lack of normal T cells was assumed. The findings that there was a decrease and altered distribution of surface markers on chronic lymphatic leukemia cells of the B- and T-cell type are discussed as further arguments referring to their clonal origin.

scholarly journals Blood kinetics, tissue distribution, and radioimaging of anti-common chronic lymphatic leukemia antigen (cCLLa) monoclonal antibody CLL2 in mice transplanted with cCLLa-bearing human leukemia cells

Blood ◽  
1990 ◽  
Vol 75 (9) ◽  
pp. 1853-1861
Author(s):  
GB Faguet ◽  
JF Agee ◽  
JT DiPiro
Keyword(s):  
Monoclonal Antibody ◽  
Specific Activity ◽  
Human Leukemia ◽  
Chronic Lymphatic Leukemia ◽  
Prolymphocytic Leukemia ◽  
Normal Tissues ◽  
Lymphatic Leukemia ◽  
Human Leukemia Cells ◽  
Glycoprotein Antigen ◽  
Leukemia Antigen

The blood kinetics and biodistribution of anti-common chronic lymphatic leukemia antigen (cCLLa) monoclonal antibody (MoAb) CLL2 were assessed in mice bearing cCLLa+ tumors. The cCLLa is a 69-Kd glycoprotein antigen expressed selectively by malignant B cells in human CLL, hairy cell leukemia (HCL), and prolymphocytic leukemia. Immunoreactive 125I- CLL2 (5 micrograms/mouse, specific activity 4.3 microCi/micrograms) was injected intravenously in mice bearing HCL-derived EH xenografts, and blood kinetics and biodistribution were ascertained up to 16 days postinjection. Radioimages were also obtained up to 72 hours after injecting 10 micrograms/mouse (specific activity 50.1 microCi/micrograms) of 125I-CLL2. Distinct 125I-CLL2 blood kinetics were observed in EH engrafted compared with tumor-free mice including: a longer 125I-CLL2 T 1/2 (153 hours v 72 hours), and a considerably greater blood clearance (173 mg/h v 54.7 mg/h) with biexponential rather than monoexponential configuration; and a greater volume of antibody distribution (31,483 mg v 5,729 mg). These data suggest more rapid tissue uptake by grafted tumours. Preferential 125I-CLL2 uptake by EH tumours relative to normal tissues was observed beginning 24 hours postinjection (mean ratio, 4.2) with average peak tumor 125I-CLL2 levels of 428.7 pg/mg. 125I-CLL2 uptake selectivity by EH tumor cells was also supported by: (1) negligible 125I-CLL2 uptake by cCLLa- Molt-4 xenografts (average 29.1 pg/mg 24 hours postinjection); (2) background uptake of cCLLa-irrelevant MoAb 131I-LEU1 by CD5- EH xenografts (average 31.4 pg/mg 48 hours postinjection); and (3) by scintigraphy. The EH xenograft mouse model might be useful to ascertain preclinically the anti-tumor effect of anti-cCLLa MoAbs and of their conjugated derivatives.

scholarly journals Subtypes of T-cell chronic lymphatic leukemia

Cancer ◽  
1983 ◽  
Vol 51 (8) ◽  
pp. 1434-1447 ◽  
Author(s):  
Dieter Huhn ◽  
Eckhard Thiel ◽  
Hans Rodt ◽  
Günter Schlimok ◽  
Harald Theml ◽  
...  
Keyword(s):  
T Cell ◽  
Chronic Lymphatic Leukemia ◽  
Lymphatic Leukemia

scholarly journals Decrease and altered distribution of human T antigen on chronic lymphatic leukemia cells of T type, suggesting a clonal origin

Blood ◽  
1976 ◽  
Vol 47 (5) ◽  
pp. 723-736
Author(s):  
E Thiel ◽  
H Rodt ◽  
D Huhn ◽  
S Thierfelder
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Sheep Erythrocyte ◽  
T Antigen ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Chronic Lymphatic Leukemia ◽  
Lymphatic Leukemia ◽  
Clonal Origin ◽  
Lymphatic Leukemia Cells

B- and T-cell markers were studied in a patient with chronic lymphocytic leukemia and erythroderma. The absence of immunoglobulin, complement receptor, and Fc receptor, and the presence of sheep erythrocyte receptor and T-cell antigen on the membrane of the leukemic cells classified them as thymus derived. Using quantitative microphotometric immunoautoradiography, surface antigen densities were measured at the cellular level with the following results: (1) The density of T-antigenic sites was less on leukemic cells compared to normal T lymphocytes. (2) The T-antigen densities of leukemic lymphocytes varied less from cell to cell forming a homogeneous peak in histograms. (3) An Ig density of normal B lymphocytes was demonstrated on the residual T-antigen-negative cells. The results were qualitatively confirmed by direct immunofluorescence and electron microscopy with peroxidase-labeled antibodies. Furthermore, the surface antigens were quantitative microcomplement fixation test which revealed reduced binding of anti-T-cell antibodies and complement, and no antiglobulin fixation on the leukemic lymphocytes. Since lymphocytes with normal T-antigen concentration could not be found among the leukemic T lymphocytes, a lack of normal T cells was assumed. The findings that there was a decrease and altered distribution of surface markers on chronic lymphatic leukemia cells of the B- and T-cell type are discussed as further arguments referring to their clonal origin.

Production and regulation of interleukin-2 in human lymphoblastic leukemias studied with T-cell monoclonal antibodies

Blood ◽  
1983 ◽  
Vol 61 (4) ◽  
pp. 781-789
Author(s):  
S Venuta ◽  
R Mertelsmann ◽  
K Welte ◽  
SP Feldman ◽  
CY Wang ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Lymphoblastic Leukemia ◽  
Interleukin 2 ◽  
Gel Filtration ◽  
Lymphatic Leukemia ◽  
Daudi Cells ◽  
Self Replication

Human leukemias are illnesses of hemopoietic stem cells that go through processes of self-replication and partial differentiation under the control of as yet largely unknown growth and differentiation factors. IL-2 is a powerful factor controlling proliferation of normal T cells. We report that acute lymphoblastic leukemias of T and non-B, non-T phenotypes produce a growth factor after mitogen stimulation. This factor is able to support the proliferation of human and murine IL-2- dependent cytotoxic cells, has a mol wt of 26,000 daltons by gel filtration, an isoelectric point of 6.6, and its biologic activity is inhibited by an anti IL-2 monoclonal antibody. This factor is, therefore, by all parameters studied very similar to IL-2 produced by normal lymphocytes. A recently developed monoclonal antibody, Pan T2, binds to normal T cells, renders T cells responsive to IL-2, and induces the release of IL-2, which in turn provides the second signal for T-cell proliferation. Mononuclear cells from acute lymphoblastic leukemia do not respond to the addition of this monoclonal antibody unless cocultured with irradiated Daudi cells. Since normal T cells do not require Daudi to produce IL-2 and since Daudi cells do not produce IL-2 under any conditions, we conclude that the cell responsible for IL- 2 production in acute lymphatic leukemia is a leukemic T cell with an altered mechanism of IL-2 production at the level of the Pan T2 binding site.

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