Mouse monoclonal antibodies against the idiotype of human B cell non‐Hodgkin lymphomas: production, characterization and use to monitor the progress of disease

Abstract

Four monoclonal anti-idiotype (Id) antibodies against B cell non-Hodgkin lymphomas have been made by a simple and rapid procedure for hybridoma production that does not use isolated Id-carrying immunoglobulin. Mice were immunized with plasma membranes from the tumor cells. Screening of hybridoma colonies using an autologous T cell line and a cell line bearing the same immunoglobulins as the malignant lymphocytes as well as the capping phenomenon on the patient's own tumor cells, allowed selection of hybridomas producing anti-Id antibodies. These anti-Id antibodies were used to demonstrate variations in the circulating malignant cell population and fluctuations in the level of circulating free Id.

Initial experience with treatment of human B cell lymphoma with anti-CD19 monoclonal antibody

“…In the case of patient 6 a mAb against the idiotype of the tumour cell immunoglobulin [24] was used to follow the serum concentration of idiotypic lg. A finorescence-inhibition assay was performed by incubating a nearly saturating amount of anti-idiotype mAb with a series of dilutions of serum samples of the patient for 30 min at 4°C before addition to idiotype-bearing tumour cells for indirect immunofluorescence.…”

Detection of Cross-Reacting Idiotypes in Sera of Lymphoma Patients by Inverse Monoclonal Radioimmunoassay

“…To enhance the practicality of this novel approach to the therapy of lymphoma, the use of anti-id to cross-reacting idio types has been proposed [3][4][5], In view of the present findings, MoAb Y7 as the only antibody reacting against the cross-reacting idiotype can be applied in the treatment of the idiotype-positive group of lym phoma patients for bone marrow transplantation and passive therapy, either cytotoxic or regulatory in na ture. The generation of a panel of anti-id which crossreact with different tumor-derived Ig in serum, may be valuable for monitoring the disease in a high pro portion of NHL patients.…”

“…Ideally, a limited panel of anti-idiotypic reagents is required which cross-reacts with the majority of idiotypes generated by malignant B cells. Efficient and discriminative detection meth ods are required, since the frequency of positive cross reactivity between the idiotypes is low, in the range of 1/13-37 nonHodgkin's lymphoma (NHL) patients [4,5]. Rankin and Hekman [4] analyzed the cross-reac tion between the idiotypes on malignant B cells in cell suspension using a fluorescence assay with mono clonal anti-id.…”

“…Efficient and discriminative detection meth ods are required, since the frequency of positive cross reactivity between the idiotypes is low, in the range of 1/13-37 nonHodgkin's lymphoma (NHL) patients [4,5]. Rankin and Hekman [4] analyzed the cross-reac tion between the idiotypes on malignant B cells in cell suspension using a fluorescence assay with mono clonal anti-id. An alternative approach has been de scribed by Stevenson et al [5], in which the level of cross-reacting idiotypic molecules is measured in pu rified extracellular Ig using an ELISA inhibition method.…”

Enhancement of the antibody-dependent cellular cytotoxicity of human peripheral blood lymphocytes with interleukin-2 and interferon α

“…Cells were incubated in the appropriate dilution of mAb [(0.5 -1) x 105 cells in 25 gl] in V-bottom 96-well microtiter plates (Greiner). For the determination of background staining the cells were incubated with mAb K8, which reacts only with the idiotype of the tumour cells of a non-Hodgkin lymphoma patient [28]. Bound mouse Ig was detected with fluorescein-isothiocyanate (FITC)-conjugated F(ab)2 fragments of goat anti-(mouse Ig) (GAM/FITC, Tago, Burlingame, Calif., USA).…”