CD3× anti‐nitrophenyl bispecific diabodies: Universal immunotherapeutic tools for retargeting T cells to tumors

Locoregional treatment of low-grade B-cell lymphoma with CD3�CD19 bispecific antibodies and CD28 costimulation: II. Assessment of cellular immune responses

“…We have recently studied the capability of “universal” CD3×anti‐hapten bispecific diabodies and B7×anti‐TAA fusion proteins to activate T lymphocytes in a highly tumor‐specific manner. We demonstrated that “universal” recombinant bispecific molecules can act in concert with a variety of hapten‐conjugated anti‐tumor ligands to induce the cytotoxic T cell mediated killing of malignant cells that display appropriate antigens on their surfaces, facilitating the application of a cocktail of different anti‐tumor ligands to eliminate potential antigen deficient tumor cells 20. Furthermore, we showed that CD3×anti‐CEA diabodies in combination with B7×anti‐CEA fusion proteins can be used to activate autologous T cell in human colon carcinoma with a high tumor‐specificity 19.…”

Future of Monoclonal Antibodies in the Treatment of Hematologic Malignancies

“…38,39 Divalent diabodies (two different singlechain Fvs noncovalently associated) are now being used for bispecific applications. 40,41 Bispecific molecules are monovalent for each antigen and hence have lower avidity than monospecific antibodies. When bispecific antibodies are administered, binding to the effector cells in the circulation rather than the tumor is a problem that must be resolved.…”

“…42 In addition, significant human anti-bispecific antibodies have been reported, 42 although the use of humanized divalent diabodies may eliminate this problem. 40,41 Several clinical trials in malignancy with bispecific MAb have been reported, the most promising being chemically linked Fabs targeting FcγRI and Her-2. 42…”