Bispecific monoclonal antibody therapy of B-cell malignancy.
Bispecific monoclonal antibodies (bsAbs) that recognize CD3 with one arm and a tumor associated antigen with the other arm can retarget T-cells toward tumor cells in an MHC independent manner, thereby combining the specificity of monoclonal antibodies with the power of the cellular immune system. B-cell malignancies are particularly attractive as targets for anti-CD3-based bsAb therapy because of their sensitivity to other forms of antibody therapy, and the extent to which B-cells and T-cells communicate at the molecular level. BsAbs that recognize CD3 and a number of antigens on malignant B-cells have been shown in vitro to be capable of retargeting T-cells. In animal models of B-cell malignancy, bsAb can eliminate tumor loads that are resistant to unmodified monoclonal antibody therapy. Ongoing early clinical trials in advanced B-cell lymphoma indicate CD3-based bsAbs have significant biologic effects, and suggest they have anti-tumor activity as well. A number of significant questions relating to bsAb therapy of B-cell malignancies remain. It is unclear what role both endogenously produced and exogenously administered cytokines are likely to play. Further exploration of whether bsAb can induce T-cells to target to tumor will also be required before the true promise of this novel form of immunotherapy can be determined.
Weiner
G J
GJ
Department of Internal Medicine, University of Iowa, Iowa City 52242, USA.
De Gast
G C
GC
D000818:Animals; D018033:Antibodies, Bispecific / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D015448:Leukemia, B-Cell / Q000188:drug therapy* / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000276:immunology
D018033:Antibodies, Bispecific