Performance of CD3xCD19 Bispecific Monoclonal Antibodies in B Cell Malignancy

Abstract

Bispecific monoclonal antibodies, with a dual specificity for tumor associated antigens on target cells and for surface markers on immune effector cells, have been shown (in vitro) to be effective in directing and triggering effector cells to kill target cells resulting in target cell lysis. Bispecific monoclonal antibodies (BsAb) against the CD3 antigen on T cells and the CD 19 anitigen on B cell were developed. Data obtained by in vitro experiments might indicate that clinical responses in BsAb im-munotherapy, will only be obtained in patients with minimal tumor load, and may need additional T cell stimulation via cytokines such as IL-2. Although these experiments have shown us their limitations, they also include the promise of BsAb-directed immunotherapy in B cell malignancy as further demonstrated during a Phase I trail, showing little toxicity. Clearly, much, remains to be done before this BsAb is routinely used for therapy, but, the results presented show that the CD3×CD19 BsAb has a potential as a therapeutic agent in B cell malignancy. This report describes the experiments performed to test a new immunotherapeutic approach for the treatment ot B cell malignancy. Bispecific antibodies are described that can target cytotoxic T cells to tumor cells and elicit a cy-tolytic action towards these cancer cells.

Key Words:

• immuriotherapy
• bispecific antibodies
• B cell malignancy
• T cell activation