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 Blood, 4 June 2009, Vol. 113, No. 23, pp. 5905-5910.
Prepublished online as a Blood First Edition Paper on March 30, 2009; DOI 10.1182/blood-2009-02-205476.

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LYMPHOID NEOPLASIA

131I anti-CD45 radioimmunotherapy effectively targets and treats T-cell non-Hodgkin lymphoma

Ajay K. Gopal1,2, John M. Pagel1,2, Jonathan R. Fromm3, Shani Wilbur2, and Oliver W. Press1,2

1 Division of Medical Oncology, Department of Medicine, University of Washington, Seattle; 2 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; and 3 Department of Laboratory Medicine, University of Washington, Seattle

Radioimmunotherapy (RIT) options for T-cell non-Hodgkin lymphomas (T-NHLs) are limited. We evaluated anti-CD45-RIT in human (h) and murine (m) T-NHL. CD45 was highly expressed on hT-NHL patient samples (median, 2.3 x 105 antigen-binding capacity units/cell) and hT-NHL cell lines (3.4 x 105 CD45 antigen-binding capacity units/cell). Biodistribution studies in hTNHL xenografts showed that 131I-labeled BC8 (anti-hCD45) delivered 154% (P = .01) and 237% (P = .002) more radioiodine to tumor sites over control antibodies at 24 hours and 48 hours, respectively. Importantly, tumor sites targeted with 131I-BC8 exhibited 2.5-fold (P = .05), 3.0-fold (P = .007), and 3.6-fold (P = .07) higher 131I retention over the nontarget organs of lungs, liver, and kidneys, respectively (24 hours). Because the clinical use of anti-hCD45 would target both T-NHL and other hematolymphoid tissues, we evaluated the ability of anti-mCD45 to target mT-NHL. mT-NHL grafts targeted with anti-mCD45 correspondingly retained 5.3 (P < .001), 5.4 (P < .001), and 8.7 (P < .001) times the radioactivity in tumor sites compared with nontarget organs of lung, liver, and kidney. 131I-labeled BC8 therapy yielded improved complete remission rates (75% vs 0%, P < .001) and progression-free survivals (median, 23 days vs 4.5 days, P < .001) compared with controls. These data indicate that the high CD45 expression of T-NHL allows reliable tumor targeting and disease control supporting anti-CD45 RIT for T-NHL patients.


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