Biomaterial Database

Studies of methotrexate-monoclonal antibody conjugates for immunotherapy. 1985

J Kanellos, and G A Pietersz, and I F McKenzie

Methotrexate (MTX) was covalently bound to two different murine monoclonal antibodies, one reactive with human colon carcinoma and the other reactive with the transferrin receptor. The drug-antibody complexes were examined for their in vitro and in vivo potency against tumors. The conditions of coupling were closely monitored, with particular attention being paid to the preservation of both drug and antibody activity. After activation of MTX with N-hydroxysuccinimide, MTX was bound to the antibodies under conditions leading to maximum protein and antibody recovery. Although the coupling conditions for both antibodies were different, up to 13 molecules of MTX-antibody molecule could be attached with retention of antibody activity. Such conjugates were active in vitro and could inhibit the growth [( 3H]deoxyuridine uptake) of cells in culture. The conjugates were highly specific, having no effect on tumors lacking the antigen; however, MTX complexed to antibody was less potent than the free drug. In vivo, the MTX-antibody impaired the growth of established tumors. Thus MTX-antibody complexes can be successfully produced and can be used for the immunotherapy of tumors.

UI	MeSH Term	Description	Entries
D007167	Immunotherapy	Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection.	Immunotherapies
D007945	Leukemia, Lymphoid	Leukemia associated with HYPERPLASIA of the lymphoid tissues and increased numbers of circulating malignant LYMPHOCYTES and lymphoblasts.	Leukemia, Lymphocytic,Lymphocytic Leukemia,Lymphoid Leukemia,Leukemias, Lymphocytic,Leukemias, Lymphoid,Lymphocytic Leukemias,Lymphoid Leukemias
D008727	Methotrexate	An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.	Amethopterin,Methotrexate Hydrate,Methotrexate Sodium,Methotrexate, (D)-Isomer,Methotrexate, (DL)-Isomer,Methotrexate, Dicesium Salt,Methotrexate, Disodium Salt,Methotrexate, Sodium Salt,Mexate,Dicesium Salt Methotrexate,Hydrate, Methotrexate,Sodium, Methotrexate
D008807	Mice, Inbred BALB C	An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research.	BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008819	Mice, Nude	Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.	Athymic Mice,Mice, Athymic,Nude Mice,Mouse, Athymic,Mouse, Nude,Athymic Mouse,Nude Mouse
D009368	Neoplasm Transplantation	Experimental transplantation of neoplasms in laboratory animals for research purposes.	Transplantation, Neoplasm,Neoplasm Transplantations,Transplantations, Neoplasm
D009369	Neoplasms	New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.	Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D011956	Receptors, Cell Surface	Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.	Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D011990	Receptors, Transferrin	Membrane glycoproteins found in high concentrations on iron-utilizing cells. They specifically bind iron-bearing transferrin, are endocytosed with its ligand and then returned to the cell surface where transferrin without its iron is released.	Transferrin Receptors,Transferrin Receptor,Receptor, Transferrin
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell