title: Selection of monoclonal antibody E48 IgG or U36 IgG for adjuvant radioimmunotherapy in head and neck cancer patients.
abstract: Preliminary data from recent clinical radioimmunoscintigraphy studies indicate that 99mTc-labelled murine monoclonal antibodies (MAbs) E48 and U36 have a similar ability to target squamous cell carcinoma of the head and neck (HNSCC) selectively. In the present study we describe additional aspects of murine and chimeric MAb (mMAb and cMAb) E48 and U36, which might influence the selection of one MAb for adjuvant radioimmunotherapy. To make direct comparison possible, ten patients received 11.2 +/- 0.3 and 11.1 +/- 0.2 mg (n = 5) or 51.1 +/- 0.1 and 51.0 +/- 0.4 mg (n = 5) of both mE48 IgG and mU36 IgG labelled with 131I and 125I simultaneously and underwent surgery 7-8 days after injection. The mean uptake of iodine-labelled mE48 IgG and mU36 was highest in tumour tissue, 8.9 +/- 8.9 and 8.2 +/- 4.4 %ID kg(-1) respectively. Tumour to non-tumour ratios for oral mucosa, skin, muscle, blood and bone marrow aspirate were 2.5, 5.5, 25.2, 4.7 and 4.0 respectively in the case of mE48 IgG and 2.3, 4.1, 21.0, 5.8 and 5.8 respectively in the case of mU36 IgG. The distribution of mMAbs E48 and U36 throughout tumours that had been collected in previous studies was heterogeneous when administered at a dose of 1 or 12 mg, and homogeneous when administered at a dose of 52 mg. Administration of mE48 IgG (1-52 mg) resulted in a human anti-mouse antibody response in 12 out of 28 patients, while for mU36 IgG (1-52 mg), this figure was three out of 18 patients. cMAb E48 was shown to be highly effective in mediating antibody-dependent cellular cytotoxicity in vitro, while cMAb U36 and mMAbs E48 and U36 were not effective at all. Rationales are provided that give priority to the start of adjuvant radioimmunotherapy trials with 186Re-labelled cMAb U36 IgG in head and neck cancer patients who are at high risk for the development of locoregional recurrences and distant metastases.
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: de Bree
authors.forename: J C
authors.initials: JC
authors.lastname: Roos
authors.forename: M A
authors.initials: MA
authors.lastname: Plaizier
authors.forename: J J
authors.initials: JJ
authors.lastname: Quak
authors.forename: G J
authors.initials: GJ
authors.lastname: van Kamp
authors.forename: W
authors.initials: W
authors.lastname: den Hollander
authors.forename: G B
authors.initials: GB
authors.lastname: Snow
authors.forename: G A
authors.initials: GA
authors.lastname: van Dongen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism* / Q000493:pharmacokinetics; D000920:Antibody-Dependent Cell Cytotoxicity; D001853:Bone Marrow / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy / Q000628:therapy*; D004306:Dose-Response Relationship, Immunologic; D006258:Head and Neck Neoplasms / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D051379:Mice; D016499:Radioimmunotherapy; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D011993:Recombinant Fusion Proteins