Antibodies For Clinical Use Research Articles

Forthcoming conferences organised by IBC technical services: Monoclonal antibodies for clinical use 28th–29th Novembre 1990 The regent crest hotel London, UK

Forthcoming conferences organised by IBC technical services: Monoclonal antibodies for clinical use 28th–29th Novembre 1990 The regent crest hotel London, UK

Abrogation of antibody responses in rats to murine monoclonal antibody 791T/36 by treatment with daunomycin-cis-aconityl-791T/36 conjugates.

The majority of monoclonal antibodies in clinical use are of murine origin. It is now well-established that patients generate an antibody response to the mouse immunoglobulin which restricts repeated administration. Pre-sensitization of patients to mouse antibody is screened by hypersensitivity to i.d. administered antibody. This study shows that low doses of mouse antibody administered either i.d. or s.c. are highly immunogenic and suggests that a serological assay would be a safer method of screening for anti-mouse antibodies. Rats treated with monoclonal antibody linked via an acid labile cis-aconityl bond to daunomycin failed to produce a primary response to this conjugate. They were also rendered immunologically unresponsive to subsequent challenges with the unconjugated monoclonal antibody. The induced state of immunological unresponsiveness to free antibody persisted in the rats for 18 weeks and although antibody-cis-aconityl-daunomycin pre-treated animals eventually responded to the fourth challenge with free antibody, at week 25, the response was still significantly less than in the free antibody-pre-treated and challenged animals. These studies show that the use of antibody-cis-aconityl-daunomycin conjugates may provide an approach for the control of human responses to mouse immunoglobulin.

In vitro measurement of avidity of radioiodinated antibodies

A determination of the ability of radiolabeled antibodies to bind to their target antigen is an essential step in the initial selection of antibodies for clinical use as well as a quality control measure. In our studies of the 131I-labeled anti-Thy 1.1 antibody treatment of murine lymphoma we have used cell binding assays with a combination of Lineweaver-Burk analysis to determine immunoreactivity and Scatchard analysis to determine antibody avidity. Both assays were systematically influenced by target cell fixation and measurement of avidity was dependent on immunoreactivity. For 131I-labeled anti-Thy 1.1 antibody, avidity was a much more sensitive indicator of iodination damage and predictor of in vivo behavior than was immunoreactivity, while for other antibodies immunoreactivity has been a better indicator of labeling damage. Thus, immunoreactivity and avidity assays are complementary and knowledge of both factors is required for the design of sensitive quality control procedures for radiolabeled antibodies.