Expression of nonspecific cross-reacting antigen species in myeloid leukemic patients and healthy subjects

Noworolska, A; Harłozińska, A; Buchegger, Franz; Lawińska, B; Richter, R. L.

doi:10.1007/bf00320651

Cited by 18 publications

(9 citation statements)

References 9 publications

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“…24,25,33,49,50 We felt that these advantageous properties outweighed potential disadvantages such as a lack of binding to myeloid leukaemic blasts. [28][29][30]32 This reliance on the crossfire effect clearly imposes certain limitations on the kinds of patients that can be treated with this approach. Thus, we restricted ourselves to treating patients in remission or PR.…”

Section: Discussionmentioning

confidence: 99%

“…[25][26][27] The CD66 antigen is expressed at a high density (2 ϫ 10 5 molecules per cell) on normal myelopoietic cells from the promyelocyte onward but not on AML blasts. [28][29][30][31] Aberrant expression is found on a significant fraction of CD10 ϩ acute lymphoblastic leukemia (ALL) blasts. 31,32 The CD66 molecule is neither internalized nor shed.…”

Section: Introductionmentioning

confidence: 99%

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Rhenium 188–labeled anti-CD66 (a, b, c, e) monoclonal antibody to intensify the conditioning regimen prior to stem cell transplantation for patients with high-risk acute myeloid leukemia or myelodysplastic syndrome: results of a phase I-II study

Bunjes

Buchmann

Duncker

et al. 2001

Blood

162

100

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The conditioning regimen prior to stem cell transplantation in 36 patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) was intensified by treating patients with a rhenium 188-labeled anti-CD66 monoclonal antibody. Dosimetry was performed prior to therapy, and a favorable dosimetry was observed in all cases. Radioimmunotherapy with the labeled antibody provided a mean of 15.3 Gy of additional radiation to the marrow; the kidney was the normal organ receiving the highest dose of supplemental radiation (mean 7.4 Gy). Radioimmunotherapy was followed by standard full-dose conditioning with total body irradiation (12 Gy) or busulfan and high-dose cyclophosphamide with or without thiotepa. Patients subsequently received a T-cell-depleted allogeneic graft from a HLA-identical family donor (n ‫؍‬ 15) or an alternative donor (n ‫؍‬ 17). In 4 patients without an allogeneic donor, an unmanipulated autologous graft was used. Infusion-related toxicity due to the labeled antibody was minimal, and no increase in treatment-related mortality due to the radioimmunoconjugate was observed. Day ؉30 and day ؉100 mortalities were 3% and 6%, respectively, and after a median follow-up of 18 months treatment-related mortality was 22%. Late renal toxicity was observed in 17% of patients. The relapse rate of 15 patients undergoing transplantation in first CR (complete remission) or second CR was 20%; 21 patients not in remission at the time of transplantation had a 30% relapse rate. (Blood. 2001;98:565-572)

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rhenium 188–labeled anti-CD66 (a, b, c, e) monoclonal antibody to intensify the conditioning regimen prior to stem cell transplantation for patients with high-risk acute myeloid leukemia or myelodysplastic syndrome: results of a phase I-II study

Bunjes

Buchmann

Duncker

et al. 2001

Blood

162

100

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“…They are expressed on myelopoietic cells beyond the maturation stage of promyelocytes. Details of the antibody/epitope interaction have been reported previously [9,12,13,14]. No internalisation or shedding occurs after mAb binding.…”

Section: Methods and Patientsmentioning

confidence: 92%

A comparison of the biodistribution and biokinetics of 99mTc-anti-CD66 mAb BW 250/183 and 99mTc-anti-CD45 mAb YTH 24.5 with regard to suitability for myeloablative radioimmunotherapy

Buchmann

Kull

Glatting

et al. 2003

Eur J Nucl Med Mol Imaging

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Radioimmunotherapy (RIT) with radiolabelled monoclonal antibodies (mAbs) is an effective method of achieving myeloablation in leukaemia patients prior to stem cell transplantation (SCT). We wished to compare the approaches of specific binding to leukaemic blasts and non-specific binding to benign red marrow cells, which results in a myeloablative "cross-fire" effect. Therefore, we prospectively evaluated the biodistribution and biokinetics of the anti-CD45 mAb YTH 24.5 and the anti-CD66 mAb BW 250/183 with regard to their suitability for myeloablative RIT. The red marrow selective anti-CD66 mAb BW 250/183 (IgG1) binds to normal granulopoietic cells. In contrast, the anti-CD45 mAb YTH 24.5 (IgG2b) binds to 85-90% of acute leukaemic blasts and almost all haematopoietic white cells. Patients with leukaemic blast infiltration of the marrow <25% and assigned for RIT and SCT were included. Twelve patients (eight male, four female; median age 46+/-7 years) with AML (5), CML (5) or ALL (2) were examined. Both mAbs were labelled with technetium-99m. Within 48 h, 906+/-209 MBq (99m)Tc-anti-CD66 mAb and 760+/-331 MBq (99m)Tc-anti-CD45 mAb were injected consecutively. Scintigraphic and urinary measurements were performed 1, 2, 4 and 24 h after injection. Serum activities were evaluated 2, 5, 10, 15, 30 and 60 min and 2, 4 and 24 h after injection. Compared with the anti-CD45 mAb, the anti-CD66 mAb showed an approximately fourfold higher accumulation in the red marrow, a 2.5-fold lower accumulation in the liver and similar accumulation in the kidneys. The serum activity (% of the injected dose) initially decreased faster for the anti-CD45 mAb but was similar for the two mAbs 24 h after injection: 3.3%+/-1.2% (anti-CD66 mAb) and 2.4%+/-1.1% (anti-CD45 mAb). The cumulated urinary excretion was 17%+/-6.6% (anti-CD66 mAb) and 27.3%+/-7.9% (anti-CD45 mAb) 24 h after application. In these patients with low tumour load, the anti-CD66 mAb BW 250/183 showed more favourable properties in terms of biodistribution and pharmacokinetics. Thus, it appears superior to anti-CD45 mAb YTH 24.5 in selectively increasing the marrow dose and avoiding extramedullary organ toxicity.

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“…Non specific cross-reacting antigen-antibody (TcNCAA) binds to granulopoetic bone marrow cells and granulocytes in peripheral blood via interaction with nonspecific cross-reacting antigen 95 (NCA-95) ( 14). NCA-95 is expressed in the cytoplasm and at the cell membrane of granulocytes as well as on mature granulopoetic bone marrow cells (16)(17)(18)(19)(20)(21). Erythropoetic, thrombopoetic and lymphatic cells did not express NCA-95 (18,20).…”

Section: Antibodymentioning

confidence: 99%

Bone Marrow Immunoscintigraphy Compared with Conventional Bone Scintigraphy for the Detection of Bone Metastases

Reske¹,

Kartsens²,

Sohn³

et al. 1993

Acta Oncologica

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Expression of nonspecific cross-reacting antigen species in myeloid leukemic patients and healthy subjects

Cited by 18 publications

References 9 publications

Rhenium 188–labeled anti-CD66 (a, b, c, e) monoclonal antibody to intensify the conditioning regimen prior to stem cell transplantation for patients with high-risk acute myeloid leukemia or myelodysplastic syndrome: results of a phase I-II study

Rhenium 188–labeled anti-CD66 (a, b, c, e) monoclonal antibody to intensify the conditioning regimen prior to stem cell transplantation for patients with high-risk acute myeloid leukemia or myelodysplastic syndrome: results of a phase I-II study

A comparison of the biodistribution and biokinetics of 99mTc-anti-CD66 mAb BW 250/183 and 99mTc-anti-CD45 mAb YTH 24.5 with regard to suitability for myeloablative radioimmunotherapy

Bone Marrow Immunoscintigraphy Compared with Conventional Bone Scintigraphy for the Detection of Bone Metastases

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