Consumption of monoclonal anti-idiotypic antibody by neoplastic B lymphocytes: A guide for immunotherapy

Emergence of immunoglobulin variants following treatment of a B cell leukemia with an immunotoxin composed of antiidiotypic antibody and saporin.

“…An additional mAb, anti-free X Id, was raised as described by Elliott et al (27), using urinary X chain isolated from L2C leukemic guinea pigs as the immunogen (29,30). In a standard ELISA (31), this antibody reacted strongly with L2C urinary X chains, weakly with guinea pig normal X chain (29) and showed no reactivity with L2C idiotypic 19 S IgM (32). Thus the epitope seen by anti-free X Id is expressed on X chain derived from the L2C tumor, but is hidden or blocked in the intact IgM molecules .…”

“…Samples of the supernatant were taken at intervals, cooled on ice, and the cells sedimented by centrifugation at 200 g for 5 min. The concentration of guinea pig Ig in the supernatants was estimated by ELISA using the method described by Stevenson et al (31). The IgM was captured from supernatant samples by adsorption binding to sheep anti-Fdu (32) that had been coated onto microplates at 20 Ag/ml and then detected with HRP-labelled sheep anti-,u chain antibody (31) at 4 ug/ml.…”

Monoclonal antibodies in clinical medicine.

“…Other monoclonals which react with tumour associated antigens include murine monoclonal antibodies against some of the antigens found in melanoma cell membranes,'2 colorectal carcinoma, ' 20 Although the production of tailor made antibody for each individual patient may seem impracticable because of the time required and the expense, potentially monoclonal antibodies could be used to modify or regulate the aberrant behaviour of some of the cells of the immune system in other disorders where dysfunction rather than malignant proliferation is the problem, such as the autoimmune diseases.2'…”

“…Even so, remarkable if short lived responses have been achieved, particularly in cutaneous T cell malignancies" and in a few B cell lymphomas with antiidiotype antibody-that is, a monoclonal antibody directed against the immunoglobin unique to the malignant clone of B cells forming the tumour. 20 Although the production of tailor made antibody for each individual patient may seem impracticable because of the time required and the expense, potentially monoclonal antibodies could be used to modify or regulate the aberrant behaviour of some of the cells of the immune system in other disorders where dysfunction rather than malignant proliferation is the problem, such as the autoimmune diseases.2'…”

Future Aspects of Cancer Treatment: The Use of Monoclonal Antibodies

“…An optimal Moab saturation of the tumor cell surface is probably critical. Stevenson et al (5) have calculated that in an animal B-cell lymphoma system at least 100 mg have to be infused to maximally saturate idiotypic determinants on 10 12 cells. As 10 12 cells represents a small tumor volume, large quantities of Moab have to be given to the patient to optimize therapy.…”