131I anti-CD45 radioimmunotherapy effectively targets and treats T-cell non-Hodgkin lymphoma - PubMed (original) (raw)

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

Ajay K Gopal et al. Blood. 2009.

Abstract

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.

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Figures

Figure 1

Mean and SDs of antigen density (ABC) of CD45 on T-NHL patient samples and T-NHL lines. formula image indicates patient samples; and ■, T-NHL lines. PTCL indicates peripheral T-cell lymphoma; ALCL, anaplastic large cell lymphoma; LBL, T-lymphoblastic leukemia/lymphoma; MF, mycosis fungoides; and NK/T, NK/T-cell lymphoma, nasal type.

Figure 2

Biodistribution of 131I-BC8 (anti-CD45) and 125I-BHV-1 (control) in a human T-NHL xenograft model. Biodistributions quantified as percentage injected radioiodine dose/g tissue (%ID/g) of 131I-BC8 (anti-CD45, ■) and 125I-BHV-1 (control, formula image ) in mice with CCRF-CEM (A,B) and Karpas 299 (C,D) xenografts after 24 and 48 hours.

Figure 3

Tumor-to-normal organ ratios of retained radioactivity following targeting of human T-NHL xenografts with 131I-BC8 (anti-CD45) and I-125-BHV-1 (control). Tumor-to-normal organ ratios of percentage injected radioiodine/g tissue of 131I-BC8 (anti-CD45, ■) and 125I-BHV-1 (control, formula image ) in mice with CCRF-CEM (A,B) and Karpas 299 (C,D) xenografts after 24 and 48 hours.

Figure 4

Biodistribution of 131I-30F11 (antimurine CD45) in a syngeneic murine T-NHL model. (A) Percentage injected 131I dose/g tissue (%ID/g) in target (■) and nontarget (▨) organs after 131I-30F11 (antimurine CD45) in an EL-4 (murine T-NHL) model. (B) The resultant tumor-to-normal organ ratios (24 hours).

Figure 5

Antitumor efficacy of 131I-BC8 (anti-CD45) in a human T-NHL xenograft model. Tumor volume (A) and progression-free survival (B) in mice bearing human T-NHL xenografts (CCRF-CEM) after no treatment, BHV1 labeled with 300 μCi 131I (control), BC8 labeled with 300 μCi 131I, or BC8 labeled with 400 μCi 131I.

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131I anti-CD45 radioimmunotherapy effectively targets and treats T-cell non-Hodgkin lymphoma - PubMed (original) (raw)