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HLA-DR monoclonal antibodies inhibit the proliferation of normal and chronic granulocytic leukaemia myeloid progenitor cells

HLA-DR monoclonal antibodies inhibit the proliferation of normal and chronic granulocytic leukaemia myeloid progenitor cells
HLA-DR monoclonal antibodies inhibit the proliferation of normal and chronic granulocytic leukaemia myeloid progenitor cells

We studied the capacity of murine monoclonal antibodies with HLA-DR specificity to inhibit the proliferation in vitro of erythroid (BFU-E and CFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells in normal bone marrow and the blood of patients with chronic granulocytic leukaemia (CGL). Two IgG2 antibodies (CA 2.06 and L243) inhibited the proliferation of normal BFU-E and CFU-GM at relatively high dilution; a third antibody, DA2, had no effect on either progenitor cell. A complement-fixing monoclonal antibody with T-cell activity (OKT3) produced only minor reduction in progenitor cel proliferation. Further studies with L243 showed that BFU-E and CFU-GM from the blood of patients with CGL were inhibited to the same degree as normal marrow progenitor cells. The inhibition of progenitor cell proliferation by a given antibody was always complement dependent and was therefore presumed to be due to a direct cytotoxic effect. The inhibitory effect of monoclonal antibodies is a valuable approach to the characterization of antigenic determinants on myeloid progenitor cells and the differential cytotoxicity of selected monoclonal antibodies might be exploitable for therapy.

Animals, Antibodies, Monoclonal, Cell Division, Colony-Forming Units Assay, Complement System Proteins, Cytotoxicity, Immunologic, HLA-DR Antigens, Hematopoietic Stem Cells, Histocompatibility Antigens Class II, Humans, Leukemia, Myeloid, Mice, Journal Article, Research Support, Non-U.S. Gov't
0007-1048
411-20
Goldman, J M
2c27a1b3-c445-4593-a6b5-2e6e749fa1cb
Hibbin, J
32069fc0-7111-4d35-b8fb-fe4f0120587e
Kearney, L
ad57b9c8-b5e2-4a77-9a11-8d1e3827e298
Orchard, K
794654ab-d6cc-488a-ac11-c9217433c7a2
Th'ng, K H
e7b00688-308a-4d35-ad1d-931a409c9b1f
Goldman, J M
2c27a1b3-c445-4593-a6b5-2e6e749fa1cb
Hibbin, J
32069fc0-7111-4d35-b8fb-fe4f0120587e
Kearney, L
ad57b9c8-b5e2-4a77-9a11-8d1e3827e298
Orchard, K
794654ab-d6cc-488a-ac11-c9217433c7a2
Th'ng, K H
e7b00688-308a-4d35-ad1d-931a409c9b1f

Goldman, J M, Hibbin, J, Kearney, L, Orchard, K and Th'ng, K H (1982) HLA-DR monoclonal antibodies inhibit the proliferation of normal and chronic granulocytic leukaemia myeloid progenitor cells. British Journal of Haematology, 52 (3), 411-20.

Record type: Article

Abstract

We studied the capacity of murine monoclonal antibodies with HLA-DR specificity to inhibit the proliferation in vitro of erythroid (BFU-E and CFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells in normal bone marrow and the blood of patients with chronic granulocytic leukaemia (CGL). Two IgG2 antibodies (CA 2.06 and L243) inhibited the proliferation of normal BFU-E and CFU-GM at relatively high dilution; a third antibody, DA2, had no effect on either progenitor cell. A complement-fixing monoclonal antibody with T-cell activity (OKT3) produced only minor reduction in progenitor cel proliferation. Further studies with L243 showed that BFU-E and CFU-GM from the blood of patients with CGL were inhibited to the same degree as normal marrow progenitor cells. The inhibition of progenitor cell proliferation by a given antibody was always complement dependent and was therefore presumed to be due to a direct cytotoxic effect. The inhibitory effect of monoclonal antibodies is a valuable approach to the characterization of antigenic determinants on myeloid progenitor cells and the differential cytotoxicity of selected monoclonal antibodies might be exploitable for therapy.

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More information

Published date: November 1982
Keywords: Animals, Antibodies, Monoclonal, Cell Division, Colony-Forming Units Assay, Complement System Proteins, Cytotoxicity, Immunologic, HLA-DR Antigens, Hematopoietic Stem Cells, Histocompatibility Antigens Class II, Humans, Leukemia, Myeloid, Mice, Journal Article, Research Support, Non-U.S. Gov't
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 411593
URI: https://eprints.soton.ac.uk/id/eprint/411593
ISSN: 0007-1048
PURE UUID: d7e623ea-1b3c-4949-bf08-4f8c8b621807
ORCID for K Orchard: ORCID iD orcid.org/0000-0003-2276-3925

Catalogue record

Date deposited: 21 Jun 2017 16:31
Last modified: 14 Mar 2019 01:45

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Contributors

Author: J M Goldman
Author: J Hibbin
Author: L Kearney
Author: K Orchard ORCID iD
Author: K H Th'ng

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