Novel antitenascin antibody with increased tumour localisation for Pretargeted Antibody-Guided RadioImmunoTherapy (PAGRIT)

Abstract

The Pretargeted Antibody-Guided RadioImmunoTherapy (PAGRIT) method is based on intravenous, sequential administration of a biotinylated antibody, avidin/streptavidin and 90 Y-labelled biotin. The hybridoma clone producing the monoclonal antitenascin antibody BC4, previously used for clinical applications, was found not suitable for further development because of the production of an additional, nonfunctional light chain. In order to solve this problem, the new cST2146 hybridoma clone was generated. The monoclonal antibody ST2146, produced by this hybridoma, having the same specificity as BC4 but lacking the nonfunctional light chain, was characterised. ST2146 was found able to bind human tenascin at an epitope strictly related, if not identical, to the antigenic epitope of BC4. It showed, compared to BC4, higher affinity and immunoreactivity and similar selectivity by immunohistochemistry. Biodistribution studies of biotinylated ST2146 and three other monoclonal antitenascin antibodies showed for ST2146 the highest and more specific tumour localisation in HT29-grafted nude mice. On the overall, ST2146 appears to be a good alternative to BC4 for further clinical development of PAGRIT.

Medullary Thyroid Carcinoma

“…Two main techniques have been tested clinically. One is based on the avidin/biotin system (De Santis et al 2003), and the other, termed affinity enhancement system, is based on the use of an unlabeled bispecific anti-tumor/anti-hapten antibody (BsMAb) which is injected first, and of a small, rapidly diffusible, radiolabeled bivalent hapten, which is injected a few days after the first injection (Barbet et al 1999). The main advantage of this technique is the avid binding of the bivalent hapten for the immunoconjugate prelocalized on the surface of target cells, whereas haptenimmunoconjugate complexes in the circulation dissociate with clearing of excess hapten through the kidneys.…”

Survey of the year 2003 commercial optical biosensor literature

“…The automation, reliability and versatility of the Biacore 2000 and 3000 make these two platforms the workhorses of biosensor technology (as shown in references 324, 384, 662, and 788, each of which we discuss in detail later in this survey). Good-quality data, however, can also be obtained using the Biacore X 70,81,261,352 and 1000. 71,264,298,448 There were a number of papers illustrating work performed using the two most recently released platforms, Biacore Q (for food analysis) 841,844,845,847,[852][853][854][855] and Biacore S51 (for rapid screening and ultra-high-resolution kinetic analyses of small molecules).…”

Targeted radiotherapy of brain tumours

“…Furthermore, it was discovered after completion of this trial that the BC-4 mAb hybridoma clone produced an additional nonfunctional light chain (De Santis et al, 2003). To solve this problem, a new anti-tenascin mAb, ST2146, has been generated.…”