![]() Two interesting targets in this context are the vascular integrins α vβ 3 and α vβ 5 for which it is still unclear if they promote or inhibit neovascularization. Overexpression of certain integrins on tumor cells, tumor stroma, or neovasculature makes these receptors attractive targets for specific cancer therapy. Integrins are a family of transmembrane heterodimer glycoprotein cell surface receptors primarily responsible for exchanging information between cells and the surface surrounding ECM. This modulation includes the release of proteases that remodel the ECM, the deposition of new ECM molecules, and alterations in the expression of cell adhesion molecules such as integrins. Modulation of crosstalk between cells and/or cell extracellular matrix (ECM) adhesive components is of key importance for the occurrence of metastasis. During cancer progression the ability to invade and metastasize is a very important aggravating factor. Tumorigenesis and cancer progression are multi-step processes. Due to their fast blood clearance, the fragments show high potential for radioimmunodiagnosis. The chF(ab') 2 fragment shows a similar receptor affinity and a faster blood clearance, causing less non-specific retention than the chAb. In vitro and in vivo properties show that the chAb 14C5 is promising for radioimmunotherapy, due to its high maximum tumor uptake and its long retention in the tumor. The chimerization of mAb 14C5 and its fragments has no or negligible effect on the properties of the antibody. ChF(ab') 2 and chFab fragments showed faster clearance from the blood compared to the intact Ab. ChAb 14C5 showed highest tumor uptake (approximately 10%ID/g) at 24 h post injection, corresponding with other high-affinity Abs. Saturation binding experiments revealed high in vitro affinity of radioiodinated chAb, F(ab') 2, and Fab, with dissociation constants ( K D) of 1.19 ± 0.19, 0.68 ± 0.10, and 2.11 ± 0.58 nM, respectively. In vivo biodistribution and pharmacokinetic characteristics were studied in A549 lung tumor-bearing Swiss Nu/Nu mice. In vitro stability, specificity, and affinity of radioiodinated chAb and fragments (Iodo-Gen method) were examined on high-expressing α vβ 5 A549 lung tumor cells. The purpose of this study was to recombinantly produce chimeric antibody (chAb) derivatives of the murine mAb 14C5 and to evaluate the in vitro and in vivo characteristics. To diminish the risk of generating a human anti-mouse antibody response in patients, chimeric variants were created. Previous studies showed that radiolabeled murine monoclonal antibody (mAb) 14C5 and its Fab and F(ab') 2 fragments, targeting α vβ 5 integrin, have promising properties for diagnostic and therapeutic applications in cancer.
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