Gopal Ajay K, Pagel John M, Fromm Jonathan R, Wilbur Shani, Press Oliver W
Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, USA.
Blood. 2009 Jun 4;113(23):5905-10. doi: 10.1182/blood-2009-02-205476. Epub 2009 Mar 30.
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 10(5) antigen-binding capacity units/cell) and hT-NHL cell lines (3.4 x 10(5) CD45 antigen-binding capacity units/cell). Biodistribution studies in hTNHL xenografts showed that (131)I-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 (131)I-BC8 exhibited 2.5-fold (P = .05), 3.0-fold (P = .007), and 3.6-fold (P = .07) higher (131)I 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. (131)I-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.
T细胞非霍奇金淋巴瘤（T-NHL）的放射免疫疗法（RIT）选择有限。我们评估了抗CD45-RIT在人（h）和鼠（m）T-NHL中的效果。CD45在hT-NHL患者样本（中位数为2.3×10⁵抗原结合能力单位/细胞）和hT-NHL细胞系（3.4×10⁵ CD45抗原结合能力单位/细胞）上高度表达。hTNHL异种移植瘤的生物分布研究表明，¹³¹I标记的BC8（抗hCD45）在24小时和48小时时分别比对照抗体向肿瘤部位输送的放射性碘多154%（P = 0.01）和237%（P = 0.002）。重要的是，¹³¹I-BC8靶向的肿瘤部位在24小时时，相对于肺、肝和肾等非靶器官，¹³¹I保留量分别高2.5倍（P = 0.05）、3.0倍（P = 0.007）和3.6倍（P = 0.07）。由于抗hCD45的临床应用会同时靶向T-NHL和其他血液淋巴组织，我们评估了抗mCD45靶向mT-NHL的能力。与肺、肝和肾等非靶器官相比，抗mCD45靶向的mT-NHL移植瘤在肿瘤部位相应地保留的放射性分别为5.3倍（P < 0.001）、5.4倍（P < 0.001）和8.7倍（P < 0.001）。与对照相比，¹³¹I标记的BC8治疗使完全缓解率提高（75%对0%，P < 0.001），无进展生存期延长（中位数为23天对4.5天，P < 0.001）。这些数据表明，T-NHL中CD45的高表达允许可靠的肿瘤靶向和疾病控制，支持抗CD45 RIT用于T-NHL患者。
