This Phase I research will test the hypothesis that an optimum, commercially viable radioimmunotherapy agent is a Y-90-radiolabeled cdr-grafted LL2 MAb, targeted against radiosensitive Non-Hodgkin's lymphoma. Y-90 is to be used because of its desirable radiophysical properties, possible use on an out-patient basis and commercial availability, while the cdr-grafted MAb has been selected in order to minimize human anti-mouse antibody response, which could preclude repeat treatment. Conjugates will be radiolabeled using a bifunctional chelate based on 2-benzyl-DTPA, since routine labeling can be performed in 93- 98 percent incorporation yields within l hour. Y-90-labeled cdr-grafted LL2 will be compared to Y-90 radiolabeled murine LL2 and to the corresponding radioiodinated antibodies for stability; in in vitro cell-binding, internalization and isotope cellular retention studies, and in vivo in animal tumor xenograft models. At the conclusion of the Phase I period, the investigators will have either confirmed the suitability of the Y-90- labeled cdr-grafted LL2 for radioimmunotherapy or decided that one of the other agents would be preferred, based on the combined cell processing and tumor targeting studies. The final goal is a clinically efficacious, commercially useful, radioimmunotherapy product.
