Radioimmunotherapy recently afforded convincing results for B-cell
non-Hodgkin's lymphoma treatment with antibody specific for
B-cell differentiation antigens. High doses of unlabeled or labeled
antibodies are necessary to saturate specific sites on normal B-cells. We thus developed a new targeting strategy, taking advantage of dual binding cooperativity, to enhance the specificity of the radioactive uptake by
tumor cells. This approach was evaluated using human
Burkitt lymphoma cells (Ramos) which express both CD10 and
CD20 antigens. Most normal cells express at most one of these two
differentiation antigens but many hematological
tumors, including most human B type
acute lymphoblastic leukemia cells, express both. Cells pretargeted with two
bispecific antibodies, one recognizing CD10 and a
histamine derivative (HSG), the other recognizing CD20 and the
DTPA-
indium complex, bind cooperatively radiolabeled mixed-
haptens (
DTPA-HSG). Increased binding (about 5-fold compared to binding to only one of CD10 or
CD20 antigens) is observed at 37 degrees C, demonstrating the feasibility of the technique. This binding enhancement is a slow process, not observed at 4 degrees C. Such a binding enhancement will increase specificity for targeting
isotopes to double
antigen positive
tumor cells compared to nontumor tissue cells bearing only one of them. This approach might be used to increase
tumor irradiation with minimal irradiation of normal cells.