Monoclonal antibody-based therapies of leukemia and lymphoma

Grossbard, ML; Press, Oliver W.; Appelbaum, FR; Bernstein, ID; Nadler, LM

doi:10.1182/blood.v80.4.863.bloodjournal804863

Blood

1992

DOI: 10.1182/blood.v80.4.863.bloodjournal804863

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Monoclonal antibody-based therapies of leukemia and lymphoma

ML Grossbard¹,

Oliver W. Press²,

FR Appelbaum³

et al.

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1996

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Cited by 6 publications

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Cell Targeting of a Pore-Forming Toxin, CytA δ-Endotoxin fromBacillus thuringiensisSubspeciesisraelensis, by Conjugating CytA with Anti-Thy 1 Monoclonal Antibodies and Insulin

Al-yahyaee

Ellar

1996

Bioconjugate Chem.

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The cytolytic protein toxin CytA was linked to two monoclonal antibodies (mAb) directed against the mouse or the rat Thy 1 antigen. The purified CytA-mAb conjugates were not toxic to either target or nontarget cells. The conjugates did bind specifically to target cells since they agglutinated the target cells but not nontarget cells. When the conjugates were treated with dithiothreitol, the released CytA was toxic to all cells tested. These results suggested that the attachment of CytA to a molecule such as the mAb prevented it from forming a pore. Another conjugate was made by linking CytA to insulin. The purified insulin-CytA conjugate bound to and intoxicated cells bearing a high number of insulin receptors. Furthermore, the conjugate was far less toxic to cells expressing a low number of insulin receptors and not toxic to a known CytA target cell line from Aedes aegypti. However, CytA released from the conjugate by reduction was toxic to all cells tested. These results suggested that the cytotoxicity exhibited by CytA in the conjugate form against cells bearing insulin receptors was mediated through insulin and that, in the conjugate form, CytA no longer shows its broad in vitro cytolytic activity. The difference in toxicity between CytA-mAb conjugates and insulin-CytA conjugate is discussed in relation to size of the ligands, the number, distribution, and mobility of the target molecules, and intracellular trafficking.

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Cell Targeting of a Pore-Forming Toxin, CytA δ-Endotoxin fromBacillus thuringiensisSubspeciesisraelensis, by Conjugating CytA with Anti-Thy 1 Monoclonal Antibodies and Insulin

Al-yahyaee

Ellar

1996

Bioconjugate Chem.

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Where do we stand with radioimmunotherapy for acute myeloid leukemia?

Walter

2022

Expert Opinion on Biological Therapy

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Autoreactive, Cytotoxic T Lymphocytes Specific for Peptides Derived from Normal B-Cell Differentiation Antigens in Healthy Individuals and Patients with B-Cell Malignancies

Grube

Rezvani

Wiestner

et al. 2004

Clinical Cancer Research

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Purpose: To investigate potential immunotherapeutic strategies in B lymphocytic malignancies we looked for CTLs recognizing CD19 and CD20 epitopes.Experimental Design: Three CD19 and CD20 peptides binding to HLA-A*0201 were identified and used to detect peptide specific CTLs by a quantitative real-time PCR to measure IFN-␥ mRNA expression in 23 healthy individuals and 28 patients (18 chronic lymphocytic leukemia (CLL), 7 follicular lymphoma, 2 acute lymphocytic leukemia, and 1 large cell lymphoma). Peptide-specific CTLs were expanded in culture with CD40-activated B cells to test lytic activity in three patients.Results: In healthy individuals, CD8 ؉ T-cell responses were detected in one to CD19 74 -82 , in three to CD20 127-135 , and three to CD20 188 -196 . Seven of 27 patients (6 with CLL) had CD8 ؉ T cells recognizing CD19 74 -82 . Seven patients responded to CD20 127-135 and three to CD20 188 -196 . All were CLL patients. CD19 74 -82 -specific CTLs from three patients were expanded over 4 weeks. These cells were HLA-A*0201 specific and lytic for peptide-loaded antigenpresenting cells but not to malignant or unpulsed B cells.Conclusions: CTLs that recognize CD19 and CD20 epitopes exist in healthy individuals and may be increased in CLL patients. They are of low avidity and require high doses of peptide for activation. Strategies to increase T-cell avidity would be necessary for T-cell immunotherapeutic approaches using the peptides studied.

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Monoclonal antibody-based therapies of leukemia and lymphoma

Cited by 6 publications

References 2 publications

Cell Targeting of a Pore-Forming Toxin, CytA δ-Endotoxin fromBacillus thuringiensisSubspeciesisraelensis, by Conjugating CytA with Anti-Thy 1 Monoclonal Antibodies and Insulin

Cell Targeting of a Pore-Forming Toxin, CytA δ-Endotoxin fromBacillus thuringiensisSubspeciesisraelensis, by Conjugating CytA with Anti-Thy 1 Monoclonal Antibodies and Insulin

Where do we stand with radioimmunotherapy for acute myeloid leukemia?

Autoreactive, Cytotoxic T Lymphocytes Specific for Peptides Derived from Normal B-Cell Differentiation Antigens in Healthy Individuals and Patients with B-Cell Malignancies

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