Monoclonal antibody internalization by tumor cells: an experimental model for potential radioimmunotherapy applications

✓ A monoclonal antibody against the surface marker IOT-10 of natural killer (NK) cells was used to investigate the presence of these cells in a series of 25 glioblastomas. In 40% of the tumors, IOT-10-positive NK cells were found in small numbers scattered among the tumor cells. The presence of IOT-10-positive NK cells was not related to the degree of lymphocytic infiltration in the tumor as demonstrated by hematoxylin and eosin staining, nor did it appear to influence the survival time of the patients studied.

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Monoclonal antibody 1F5 (anti-CD20) serotherapy of human B cell lymphomas

Blood ◽

10.1182/blood.v69.2.584.584 ◽

1987 ◽

Vol 69 (2) ◽

pp. 584-591 ◽

Cited By ~ 246

Author(s):

OW Press ◽

F Appelbaum ◽

JA Ledbetter ◽

PJ Martin ◽

J Zarling ◽

...

Keyword(s):

Monoclonal Antibody ◽

Lymph Node ◽

B Cell ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

B Cell Lymphomas ◽

Antigenic Modulation ◽

Minor Response ◽

High Doses ◽

Anti Cd20

Abstract Four patients with refractory malignant B cell lymphomas were treated with continuous intravenous (IV) infusions of murine monoclonal antibody (MoAb) 1F5 (anti-CD20) over five to ten days. Dose-dependent levels of free serum 1F5 were detected in all patients. Two patients had circulating tumor cells and in both cases 90% of malignant cells were eliminated from the blood stream within four hours of initiation of serotherapy. Antigenic modulation did not occur, and sustained reduction of circulating tumor cells was observed throughout the duration of the infusions. Serial bone marrow aspirations and lymph node biopsies were examined by immunoperoxidase and immunofluorescence techniques to ascertain MoAb penetration into extravascular sites. High doses (100 to 800 mg/m2/d and high serum 1F5 levels (13 to 190 micrograms/mL) were required to coat tumor cells in these compartments in contrast to the low doses that were adequate for depletion of circulating cells. Clinical response appeared to correlate with dose of MoAb administered with progressive disease (52 mg), stable disease (104 mg), minor response (1,032 mg), and partial response (2,380 mg) observed in consecutive patients. The patient treated with the highest 1F5 dose achieved a 90% reduction in evaluable lymph node disease, but the duration of this remission was brief (six weeks). This study demonstrates that high doses of 1F5 can be administered to patients with negligible toxicity by continuous infusion and that clinical responses can be obtained in patients given greater than 1 g of unmodified antibody over a ten-day period.

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Alteration of plasma membrane of drug-resistant tumor cells: 230-Kilodalton protein identified by monoclonal antibody

Biochemical and Biophysical Research Communications ◽

10.1016/0006-291x(83)90655-1 ◽

1983 ◽

Vol 114 (3) ◽

pp. 969-975 ◽

Cited By ~ 9

Author(s):

Yoshikazu Sugimoto ◽

Hideo Suzuki ◽

Nobuo Tanaka

Keyword(s):

Monoclonal Antibody ◽

Plasma Membrane ◽

Tumor Cells ◽

Drug Resistant

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Monoclonal antibody 2C5-mediated binding of liposomes to brain tumor cells in vitro and in subcutaneous tumor model in vivo

Journal of Drug Targeting ◽

10.1080/10611860500286239 ◽

2005 ◽

Vol 13 (6) ◽

pp. 337-343 ◽

Cited By ~ 20

Author(s):

Bhawna Gupta ◽

Tatiana S. Levchenko ◽

Dmitry A. Mongayt ◽

Vladimir P. Torchilin

Keyword(s):

Monoclonal Antibody ◽

Brain Tumor ◽

Tumor Cells ◽

Tumor Model ◽

Subcutaneous Tumor ◽

Brain Tumor Cells

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Toward targeted photodynamic therapy

Pure and Applied Chemistry ◽

10.1351/pac-con-11-01-05 ◽

2011 ◽

Vol 83 (4) ◽

pp. 733-748 ◽

Cited By ~ 24

Author(s):

David Phillips

Keyword(s):

Monoclonal Antibody ◽

Photodynamic Therapy ◽

Mouse Model ◽

Tumor Cells ◽

Water Solubility ◽

Human Tumor ◽

Antibody Fragments ◽

Cell Kill ◽

Pyropheophorbide A ◽

Porphyrin Dimer

The sensitizers in common use for photodynamic therapy (PDT) are summarized, and approaches to the improvement of these outlined. Selectivity in the targeting of sensitizers to tumor cells and tissue is highly desirable, as is water solubility and prevention of aggregation. Some new free sensitizers are described, based upon the pyropheophorbide a (PPa) structure, and their photophysical properties, distribution in cells via confocal fluorescence microscopy, and cell kill properties described. A novel approach to targeting is to covalently attach such sensitizers to monoclonal antibody fragments, and recent work on the attachment of pyropheophorbide a to such monoclonal antibody fragments is reviewed, with a demonstration of the increased efficiency of cell kill, and the treatment of a solid human tumor in a mouse model described. Finally, an alternative method of achieving selectivity based upon two-photon excitation (TPE) using porphyrin dimer sensitizers is reviewed, and the use of these to kill tumor cells is compared with the use of a commercially available PDT sensitizer (Visudyne). TPE of a porphyrin dimer sensitizer is shown to be capable of sealing blood vessels in a mouse model.

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