Antigenic Modulation* *The author's work is supported by NCI grant CA 08748 and a grant from the John A. Hartford Foundation, Inc.

1970 ◽  
pp. 225-227
Author(s):  
EDWARD A. BOYSE ◽  
LLOYD J. OLD ◽  
ELISABETH STOCKERT
Keyword(s):  
Antigenic Modulation

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

Blood ◽  
1987 ◽  
Vol 69 (2) ◽  
pp. 584-591 ◽  
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.

scholarly journals Antigenic modulation limits the effector cell mechanisms employed by type I anti-CD20 monoclonal antibodies

Blood ◽  
2015 ◽  
Vol 125 (12) ◽  
pp. 1901-1909 ◽  
Author(s):  
Thomas R. W. Tipton ◽  
Ali Roghanian ◽  
Robert J. Oldham ◽  
Matthew J. Carter ◽  
Kerry L. Cox ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Natural Killer Cell ◽  
Natural Killer ◽  
Effector Cell ◽  
Killer Cell ◽  
Type I ◽  
Antigenic Modulation ◽  
Effector Mechanism ◽  
Key Points ◽  
Anti Cd20

Key Points Antigenic modulation significantly impacts natural killer cell and macrophage ability to mediate Fc γ receptor-dependent killing. hIgG1 mAbs are unable to elicit natural killer–mediated ADCC in the mouse, supporting ADCP as the dominant effector mechanism.

The Role of Cytokines in the Modulation of Cell Surface Antigens of Human Melanoma

1993 ◽  
Vol 8 (3) ◽  
pp. 151-154 ◽  
Author(s):  
A. Anichini ◽  
R. Mortarini ◽  
G. Parmiani
Keyword(s):  
Cell Surface ◽  
Surface Antigens ◽  
Surface Structures ◽  
Biological Behavior ◽  
Cell Surface Antigens ◽  
Membrane Expression ◽  
Neoplastic Cells ◽  
Antigenic Modulation ◽  
Human Malignant Melanoma ◽  
Cell Surface Structures

A number of different cytokines, including IL-1α. and ß, IL-2, IL-3, IL-4, IL-6, IL-7, IL-8, IFN-α, -ß and γ, TNF-α -ß, and TGF-ß1, can modulate the expression of distinct cell surface antigens of normal and neoplastic cells. Both induction/increase of expression and reduction of expression can be achieved depending on the antigen and on the cytokine. Antigens subjected to the modulating activity of cytokines include distinct families of cell surface structures such as the molecules coded by the major histocompatibility complex (MHC), the superfamily of adhesion receptors that regulate cell-cell and cell-matrix interaction, receptors for cytokines and growth factors and tumor-associated antigens. The modulating activity of cytokines is a consequence of their influence on gene expression, protein synthesis, membrane expression and shedding of antigens from the cell surface. The changes of phenotype due to the action of cytokines can influence the signalling pathways dependent on the expression and function of cell surf ace structures. Therefore, the antigen modulating activity of cytokines can thoroughly affect the biological behavior of normal and neoplastic cells. As described here, most of the modulating effects of cytokines on different cell surface structures and the functional consequences of antigenic modulation can be verified in human malignant melanoma cells.

scholarly journals Antigenic modulation limits the efficacy of anti-CD20 antibodies: implications for antibody selection

Blood ◽  
2010 ◽  
Vol 115 (25) ◽  
pp. 5191-5201 ◽  
Author(s):  
Stephen A. Beers ◽  
Ruth R. French ◽  
H. T. Claude Chan ◽  
Sean H. Lim ◽  
Timothy C. Jarrett ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Type I ◽  
Type Ii ◽  
Antigenic Modulation ◽  
Lymphatic Leukemia ◽  
Human B Cells ◽  
Anti Cd20

Abstract Rituximab, a monoclonal antibody that targets CD20 on B cells, is now central to the treatment of a variety of malignant and autoimmune disorders. Despite this success, a substantial proportion of B-cell lymphomas are unresponsive or develop resistance, hence more potent anti-CD20 monoclonal antibodies (mAbs) are continuously being sought. Here we demonstrate that type II (tositumomab-like) anti-CD20 mAbs are 5 times more potent than type I (rituximab-like) reagents in depleting human CD20 Tg B cells, despite both operating exclusively via activatory Fcγ receptor–expressing macrophages. Much of this disparity in performance is attributable to type I mAb-mediated internalization of CD20 by B cells, leading to reduced macrophage recruitment and the degradation of CD20/mAb complexes, shortening mAb half-life. Importantly, human B cells from healthy donors and most cases of chronic lymphatic leukemia and mantle cell lymphoma, showed rapid CD20 internalization that paralleled that seen in the Tg mouse B cells, whereas most follicular lymphoma and diffuse large B-cell lymphoma cells were far more resistant to CD20 loss. We postulate that differences in CD20 modulation may play a central role in determining the relative efficacy of rituximab in treating these diseases and strengthen the case for focusing on type II anti-CD20 mAb in the clinic.

Interaction of mAb to angiotensin-converting enzyme (ACE) with antigen in vitro and in vivo: antibody targeting to the lung induces ACE antigenic modulation

1994 ◽  
Vol 6 (8) ◽  
pp. 1153-1160 ◽  
Author(s):  
Sergei Danilov ◽  
Elena Atochina ◽  
Holger Hiemisch ◽  
Tatiana Churak-ova ◽  
Aygul Moldobayeva ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Antigenic Modulation ◽  
Antibody Targeting

scholarly journals Monoclonal antibody T101 in T cell malignancies: a clinical, pharmacokinetic, and immunologic correlation

Blood ◽  
1986 ◽  
Vol 68 (3) ◽  
pp. 752-761 ◽  
Author(s):  
JH Bertram ◽  
PS Gill ◽  
AM Levine ◽  
D Boquiren ◽  
FM Hoffman ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
T Cell ◽  
Complete Remission ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Rapid Infusion ◽  
Antigenic Modulation ◽  
T Cell Malignancies ◽  
Antibody Excess

Abstract Eight patients with cutaneous T cell lymphomas (CTCL) and five with various other T cell malignancies were treated with mouse monoclonal antibody (MoAb) T101. Doses of 1 to 500 mg were administered weekly over a two-hour period and resulted in one complete remission (convoluted T cell lymphoma) and one partial remission (CTCL). Remission duration was 6 weeks and 3 months, respectively. Frequent toxicities were pruritus, hives, flushing, and shortness of breath. Supraventricular arrhythmias and blood pressure instability were also observed. Complete targeting of peripheral blood T cells was achieved with 1 mg of MoAb in the nonleukemic patients (WBC less than 10,000/microL), and free, bioavailable antibody was present at the next (10-mg) dose level. Even higher doses resulted in substantial antibody excess that persisted for as long as 6 weeks. Serum concentrations of MoAb decreased with increasing number of peripheral blood T cells, and 25 to 35 mg of T101 were required for induction of antibody excess in leukemic patients. Excess antibody induced antigenic modulation, which was of consequence only if MoAb excess persisted to the next treatment. In the original treatment, the rapidly administered MoAb was able to target and remove peripheral blood T cells before the development of antigenic modulation. Antimouse antibodies developed in three patients. Their presence rendered further therapy ineffective and was associated with an anaphylactic reaction in one patient. Development of these antibodies could not be predicted by lymphoproliferative assays. In these assays, however, the T101 protein strongly stimulated the mononuclear cells of the patient who reached the only complete remission of this trial. Immunologic stimulation by the MoAb thus might have played a role in this patient's antitumor response. In summary, therapy with MoAb T101 was specific but only modestly efficacious. Rapid infusion of nonmodulating doses of antibody provided excellent targeting and removal of peripheral blood T cells and might be a valid approach in future trials with immunoconjugated T101.

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