In vivo effects of murine hybridoma monoclonal antibody in a patient with T-cell leukemia

Abstract A murine monoclonal antibody directed against a normal T-cell differentiation antigen was given to a patient with adult T-cell leukemia. Immunofluorescence staining showed increased amounts of this antigen on the patient's leukemia cells. Using a competition radioimmunoassay, free antigen was not detectable in the serum prior to therapy. Two courses of in vivo therapy were given using a 1-mg dose. Each produced a prompt and dramatic fall in WBC with return to pretreatment levels over the ensuing 24 hr, a pattern similar to that seen with leukopheresis. After the first dose of antibody, circulating free antigen became detectable in the serum and a transient decline in creatinine clearance was noted. A 5-mg dose of antibody given at that time was ineffective, presumably because it was blocked by free antigen. Antigenic modulation by leukemia cells was found transiently following each course of antibody. A weak and clinically insignificant host antimouse antibody response was found 5 days after the first treatment. The patient tolerated antibody therapy without difficulty. Monoclonal antibodies offer promise as an immunotherapeutic approach to cancer but problems encountered here must be addressed.

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In vivo effects of murine hybridoma monoclonal antibody in a patient with T-cell leukemia

Blood ◽

10.1182/blood.v58.1.78.bloodjournal58178 ◽

1981 ◽

Vol 58 (1) ◽

pp. 78-86

Author(s):

RA Miller ◽

DG Maloney ◽

J McKillop ◽

R Levy

Keyword(s):

Monoclonal Antibody ◽

T Cell ◽

Antibody Therapy ◽

Leukemia Cells ◽

T Cell Leukemia ◽

Cell Leukemia ◽

Antigenic Modulation ◽

Adult T Cell Leukemia ◽

Free Antigen

A murine monoclonal antibody directed against a normal T-cell differentiation antigen was given to a patient with adult T-cell leukemia. Immunofluorescence staining showed increased amounts of this antigen on the patient's leukemia cells. Using a competition radioimmunoassay, free antigen was not detectable in the serum prior to therapy. Two courses of in vivo therapy were given using a 1-mg dose. Each produced a prompt and dramatic fall in WBC with return to pretreatment levels over the ensuing 24 hr, a pattern similar to that seen with leukopheresis. After the first dose of antibody, circulating free antigen became detectable in the serum and a transient decline in creatinine clearance was noted. A 5-mg dose of antibody given at that time was ineffective, presumably because it was blocked by free antigen. Antigenic modulation by leukemia cells was found transiently following each course of antibody. A weak and clinically insignificant host antimouse antibody response was found 5 days after the first treatment. The patient tolerated antibody therapy without difficulty. Monoclonal antibodies offer promise as an immunotherapeutic approach to cancer but problems encountered here must be addressed.

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Diffuse panbronchiolitis after humanized anti-CCR4 monoclonal antibody therapy for relapsed adult T-cell leukemia/lymphoma

International Journal of Hematology ◽

10.1007/s12185-013-1278-z ◽

2013 ◽

Vol 97 (3) ◽

pp. 430-432 ◽

Cited By ~ 11

Author(s):

Koji Kato ◽

Toshihiro Miyamoto ◽

Akihiko Numata ◽

Takashi Nakaike ◽

Hideyo Oka ◽

...

Keyword(s):

Monoclonal Antibody ◽

T Cell ◽

Antibody Therapy ◽

Monoclonal Antibody Therapy ◽

T Cell Leukemia ◽

Cell Leukemia ◽

Diffuse Panbronchiolitis ◽

Adult T Cell Leukemia

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Proteasome inhibitor, bortezomib, potently inhibits the growth of adult T-cell leukemia cells both in vivo and in vitro

Leukemia ◽

10.1038/sj.leu.2403400 ◽

2004 ◽

Vol 18 (8) ◽

pp. 1357-1363 ◽

Cited By ~ 83

Author(s):

Y Satou ◽

K Nosaka ◽

Y Koya ◽

J-i Yasunaga ◽

S Toyokuni ◽

...

Keyword(s):

T Cell ◽

Proteasome Inhibitor ◽

Leukemia Cells ◽

T Cell Leukemia ◽

Cell Leukemia ◽

Adult T Cell Leukemia

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Expression of P-glycoprotein in adult T-cell leukemia cells

Blood ◽

10.1182/blood.v76.10.2065.bloodjournal76102065 ◽

1990 ◽

Vol 76 (10) ◽

pp. 2065-2071 ◽

Cited By ~ 1

Author(s):

Y Kuwazuru ◽

S Hanada ◽

T Furukawa ◽

A Yoshimura ◽

T Sumizawa ◽

...

Keyword(s):

Monoclonal Antibody ◽

T Cell ◽

Multidrug Resistant ◽

Leukemia Cells ◽

T Cell Leukemia ◽

Cell Leukemia ◽

Glycoprotein P ◽

Adult T Cell Leukemia ◽

P Glycoprotein ◽

Mdr1 Mrna

We have examined the expression of P-glycoprotein (P-gp) in adult T- cell leukemia (ATL) samples from 25 patients. Based on immunoblotting with a monoclonal antibody against P-gp, C219, 8 of 20 ATL patients were P-gp positive at the initial presentation. All 6 patients at the relapsed stage were P-gp positive, and refractory to chemotherapy. The expression of MDR1 mRNA in P-gp-positive ATL cells was increased at the relapsed stage of one patient. P-gp of this patient was photolabeled with [3H]azidopine and the labeling was inhibited with nimodipine, vinblastine and progesterone. These results suggest that P-gp expressed in ATL cells from patients at relapsed stage has the same binding site(s) for the drugs as that in multidrug resistant cells, and is correlated with the refractory nature of the cells to chemotherapy.

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Expression of P-glycoprotein in adult T-cell leukemia cells

Blood ◽

10.1182/blood.v76.10.2065.2065 ◽

1990 ◽

Vol 76 (10) ◽

pp. 2065-2071 ◽

Cited By ~ 88

Author(s):

Y Kuwazuru ◽

S Hanada ◽

T Furukawa ◽

A Yoshimura ◽

T Sumizawa ◽

...

Keyword(s):

Monoclonal Antibody ◽

T Cell ◽

Multidrug Resistant ◽

Leukemia Cells ◽

T Cell Leukemia ◽

Cell Leukemia ◽

Glycoprotein P ◽

Adult T Cell Leukemia ◽

P Glycoprotein ◽

Mdr1 Mrna

Abstract We have examined the expression of P-glycoprotein (P-gp) in adult T- cell leukemia (ATL) samples from 25 patients. Based on immunoblotting with a monoclonal antibody against P-gp, C219, 8 of 20 ATL patients were P-gp positive at the initial presentation. All 6 patients at the relapsed stage were P-gp positive, and refractory to chemotherapy. The expression of MDR1 mRNA in P-gp-positive ATL cells was increased at the relapsed stage of one patient. P-gp of this patient was photolabeled with [3H]azidopine and the labeling was inhibited with nimodipine, vinblastine and progesterone. These results suggest that P-gp expressed in ATL cells from patients at relapsed stage has the same binding site(s) for the drugs as that in multidrug resistant cells, and is correlated with the refractory nature of the cells to chemotherapy.

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Identification of differentially expressed molecules in adult T-cell leukemia cells proliferating in vivo

Cancer Science ◽

10.1111/j.1349-7006.2004.tb03224.x ◽

2004 ◽

Vol 95 (5) ◽

pp. 411-417 ◽

Cited By ~ 18

Author(s):

Hikari Koga ◽

Kazunori Imada ◽

Maki Ueda ◽

Masakatsu Hishizawa ◽

Takashi Uchiyama

Keyword(s):

T Cell ◽

Differentially Expressed ◽

Leukemia Cells ◽

T Cell Leukemia ◽

Cell Leukemia ◽

Adult T Cell Leukemia

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Effective therapy for a murine model of adult T-cell leukemia with the humanized anti-CD2 monoclonal antibody, MEDI-507

Blood ◽

10.1182/blood-2002-11-3601 ◽

2003 ◽

Vol 102 (1) ◽

pp. 284-288 ◽

Cited By ~ 49

Author(s):

Zhuo Zhang ◽

Meili Zhang ◽

Jeffrey V. Ravetch ◽

Carolyn Goldman ◽

Thomas A. Waldmann

Keyword(s):

Monoclonal Antibody ◽

T Cell ◽

Polymorphonuclear Leukocytes ◽

Prolonged Treatment ◽

Control Group ◽

T Cell Leukemia ◽

Cell Leukemia ◽

Adult T Cell Leukemia ◽

Tumor Killing

Abstract Adult T-cell leukemia (ATL) develops in a small proportion of individuals infected with the retrovirus human T-cell leukemia virus (HTLV-1). We evaluated the efficacy of MEDI-507 (a humanized monoclonal antibody directed against CD2) alone and in combination with humanized anti-Tac (HAT) directed toward CD25, the interleukin-2 receptor α (IL-2Rα) using a human adult T-cell leukemia xenograft model. Weekly treatments (4) with HAT significantly prolonged the survival of the ATL-bearing mice when compared with phosphate-buffered saline (PBS)–treated controls (P < .0001). Mice treated with MEDI-507 (100 μg/wk for 4 weeks) survived longer than those treated with HAT (P < .0025). Furthermore, prolonged treatment (6 months) of ATL with MEDI-507 significantly improved the outcome when compared with a short course (4 weeks) of therapy (P < .0036). Such treatment with weekly MEDI-507 for 6 months led to a prolonged survival of the ATL-bearing mice that was comparable with the survival observed in the control group of mice that did not receive a tumor or therapeutic agent. We also found that the expression of Fcγ receptors (FcRγ) on polymorphonuclear leukocytes and monocytes was required for MEDI-507–mediated tumor killing in vivo. Thus, the tumor-killing mechanism with MEDI-507 in vivo required the expression of the receptor FcRγIII on polymorphonuclear leukocytes and monocytes, suggesting that it is mediated by a form of antibody-dependent cellular cytotoxicity. These results demonstrate that MEDI-507 has therapeutic efficacy on ATL in vivo and provides support for a clinical trial involving this monoclonal antibody in the treatment of patients with CD2-expressing leukemias and lymphomas. (Blood. 2003; 102:284-288)

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