Radioimmunotherapy of B-Cell Lymphoma with [¹³¹I]Anti-B1 (Anti-CD20) Antibody

Abstract

Radioimmunotherapy with [131I]anti-B1 antibody is a promising new treatment for lymphoma.

Radioimmunotherapy for B-cell lymphoma: Y90 ibritumomab tiuxetan and I131 tositumomab

“…I 131 tositumomab efficacy data: recurrent and refractory disease Early clinical trials with I 131 tositumomab, performed at the University of Michigan, established the maximum-tolerated total body dose (Kaminski et al, 1993) and the benefit of predosing with unlabelled antibody, remarkable in this first report of 10 patients, six responded. A later report of 34 patients with mixed histologies confirmed the initial promising activity and documented the durability of some remissions (Kaminski et al, 1996).…”

“…I 131 has dual b-and g-emission properties, allowing both therapy and dosimetry to be performed with a single radioisotope. An unlabelled predose of tositumomab (450 mg) is given on day 0 to saturate nonspecific binding sites and antigen sinks (Buchsbaum et al, 1992a;Kaminski et al, 1993). This is followed by infusion of a small tracer dose of 5 mCi I 131 tositumomab (35 mg antibody).…”

“…From this the I 131 activity of the for the total body dose may be derived (Wahl, 2003). The maximum tolerated whole body dose was established as 75 cGy in the phase I study, limited by haematological toxicity, with attenuation to 65 cGy in those patients with relative thrombocytopenia (platelets 100-149 Â 10 9 /l) (Kaminski et al, 1993(Kaminski et al, , 1996. The therapeutic step is performed at days 8-14, where a further infusion of unlabelled tositumomab is followed by the patient-specific whole body dose of I 131 tositumomab.…”

Monoclonal antibodies as therapeutic agents in oncology and antibody gene therapy

“…An ORR of 71% was achieved in a trial with 59 patients with relapsed or refractory advanced lymphoma. Median survival of responders was 12 months [28]. In a trial enrolling 24 patients with relapsed low-grade NHL, a myeloablative dose of 131 I-tositumomab was administered.…”

Novel radiolabeled antibody conjugates

“…Perhaps the responses are augmented to some degree by an underlying synergy between the unconjugated and radioconjugated antibodies (Hernandez and Knox, 2004). Indeed, objective responses have been observed in lymphoma with radiolabeled antibodies having low radioactivity or low doses of antibody given, and in some cases without an ability to visualize targeting to a given lesion (Goldenberg et al, 1991;Kaminski et al, 1993;Sharkey et al, 2003a). Most of the antibodies used as radioconjugates for solid tumors have not been therapeutically active as unconjugated antibodies, and therefore there have been a variety of approaches taken to enhance the therapeutic response (Sharkey and Goldenberg, 2005).…”