Cancer Institute A national cancer institute
designated cancer center

Susan Knox

Publication Details

  • Phase 1 trial of a novel anti-CD20 fusion protein in pretargeted radioimmunotherapy for B-cell non-Hodgkin lymphoma BLOOD Forero, A., Weiden, P. L., Vose, J. M., Knox, S. J., LoBuglio, A. F., Hankins, J., Goris, M. L., Picozzi, V. J., Axworthy, D. B., Breitz, H. B., Sims, R. B., Ghalie, R. G., Shen, S., Meredith, R. F. 2004; 104 (1): 227-236

    Abstract:

    Pretargeted radioimmunotherapy (PRIT) has the potential to increase the dose of radionuclide delivered to tumors while limiting radiation to normal tissues. The purpose of this phase 1 trial is to assess safety of this multistep approach using a novel tetrameric single-chain anti-CD20-streptavidin fusion protein (B9E9FP) as the targeting moiety in patients with B-cell non-Hodgkin lymphoma (NHL), and to characterize its pharmacokinetics and immunogenicity. All patients received B9E9FP (160 mg/m(2) or 320 mg/m(2)); either 48 or 72 hours later, a synthetic clearing agent (sCA) was administered (45 mg/m(2)) to remove circulating unbound B9E9FP. (90)Yttrium ((90)Y; 15 mCi/m(2))/(111)In (5 mCi)-DOTA-biotin was injected 24 hours later. There were 15 patients enrolled in the study. B9E9FP had a mean plasma half-life (T(1/2)) of 25 +/- 6 hours with a reduction in plasma level of more than 95% within 6 hours of sCA administration. (90)Y/(111)In-DOTA-biotin infusion resulted in rapid tumor localization and urinary excretion. The ratio of average tumor to whole-body radiation dose was 49:1. No significant hematologic toxicities were noted in 12 patients. There were 2 patients who had hematologic toxicity related to progressive disease. There were 2 complete remissions (90 and 325 days) and one partial response (297 days). B9E9FP performs well as the targeting component of PRIT with encouraging dosimetry, safety, and efficacy. A dose escalation trial of (90)Y-DOTA-biotin in this format is warranted.

    View details for DOI 10.1182/blood-2003-09-3284

    View details for Web of Science ID 000222307500042

    View details for PubMedID 14996706

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