PMID: 9177472Apr 1, 1997Paper

Rapid elimination of mouse/human chimeric monoclonal antibodies in nude mice

Cancer Immunology, Immunotherapy : CII
F B van GogG A M S van Dongen

Abstract

At our laboratory we are currently evaluating the suitability of mouse/human chimeric monoclonal antibodies (cmAb) for use in radioimmunotherapy of patients with head and neck squamous cell carcinoma (HNSCC). We have developed cmAb containing the human constant IgG1 domain and the variable domains of murine mAb (mmAb) E48 and U36 respectively. We considered the tumour-bearing nude mouse to be a well-validated model for a first testing of the targeting capabilities of these cmAb in comparison with the mmAb. Therefore, 3 microg cmAb E48 (labelled with (125)I) and 3 microg mmAb E48 (labelled with (131)I) were simultaneously injected into HNSCC-bearing nude mice and, at various assay times, mAb uptake in blood and other tissues was assessed. Remarkably, while in roughly 50% of the animals the biodistribution of the conjugates was similar, in the other animals cmAb E48 showed a much higher blood clearance than mmAb E48. This resulted in a lower tumour uptake of cmAb E48 in comparison with mmAb E48. To determine whether this phenomenon was related to mAb E48 or to the animal model, other cmAb-mmAb combinations were evaluated in the same way: cmAbs SF-25, 17-1A and U36 (all IgG1) were tested and all showed a rapid elimination in about...Continue Reading

Citations

May 7, 2002·International Journal of Cancer. Journal International Du Cancer·Iris VerelGuus A M S van Dongen
May 27, 2014·European Journal of Nuclear Medicine and Molecular Imaging·Jürgen GrünbergRoger Schibli
May 21, 2008·European Journal of Nuclear Medicine and Molecular Imaging·Lars R PerkGuus A M S van Dongen
Jul 13, 2002·International Journal of Cancer. Journal International Du Cancer·Stefanie NaundorfTorsten Dreier
May 25, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Santhi GorantlaLarisa Y Poluektova
Dec 5, 2015·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Samantha Y A TerryPeter Laverman

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