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

De Santis R, Anastasi AM, D'Alessio V, Pelliccia A, Albertoni C, Rosi A, Leoni B, Lindstedt R, Petronzelli F, Dani M, Verdoliva A, Ippolito A, Campanile N, Manfredi V, Esposito A, Cassani G, Chinol M, Paganelli G, Carminati P - Br. J. Cancer (2003)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Immunology Department, Sigma Tau SpA R&D, Pomezia, Rome, Italy. rita.desantis@sigma-tau.it

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.

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BiaCore analysis of ST2146, BC4, BC2 and ST1897 on tenascin-coated chip. (A) Sensograms of indicated Mabs. All antibodies were injected at concentrations of 500, 250, 62.5, 15.6 and 3.9 nM for 60 s. The dissociation rates of the Mabs were determined over a time of 120 s. (B) Comparison of the binding and dissociation of the indicated Mabs at an injected concentration of 500 nM. (C) ka1, kd1, KD1 and χ2 of the fitted curves.
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fig5: BiaCore analysis of ST2146, BC4, BC2 and ST1897 on tenascin-coated chip. (A) Sensograms of indicated Mabs. All antibodies were injected at concentrations of 500, 250, 62.5, 15.6 and 3.9 nM for 60 s. The dissociation rates of the Mabs were determined over a time of 120 s. (B) Comparison of the binding and dissociation of the indicated Mabs at an injected concentration of 500 nM. (C) ka1, kd1, KD1 and χ2 of the fitted curves.

Mentions: The affinities of ST2146, BC4, BC2 and ST1897 were evaluated by BIAcore on a tenascin-coated chip. The sensorgrams as well as the kinetic values of Figure 5Figure 5


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

De Santis R, Anastasi AM, D'Alessio V, Pelliccia A, Albertoni C, Rosi A, Leoni B, Lindstedt R, Petronzelli F, Dani M, Verdoliva A, Ippolito A, Campanile N, Manfredi V, Esposito A, Cassani G, Chinol M, Paganelli G, Carminati P - Br. J. Cancer (2003)

BiaCore analysis of ST2146, BC4, BC2 and ST1897 on tenascin-coated chip. (A) Sensograms of indicated Mabs. All antibodies were injected at concentrations of 500, 250, 62.5, 15.6 and 3.9 nM for 60 s. The dissociation rates of the Mabs were determined over a time of 120 s. (B) Comparison of the binding and dissociation of the indicated Mabs at an injected concentration of 500 nM. (C) ka1, kd1, KD1 and χ2 of the fitted curves.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376359&req=5

fig5: BiaCore analysis of ST2146, BC4, BC2 and ST1897 on tenascin-coated chip. (A) Sensograms of indicated Mabs. All antibodies were injected at concentrations of 500, 250, 62.5, 15.6 and 3.9 nM for 60 s. The dissociation rates of the Mabs were determined over a time of 120 s. (B) Comparison of the binding and dissociation of the indicated Mabs at an injected concentration of 500 nM. (C) ka1, kd1, KD1 and χ2 of the fitted curves.
Mentions: The affinities of ST2146, BC4, BC2 and ST1897 were evaluated by BIAcore on a tenascin-coated chip. The sensorgrams as well as the kinetic values of Figure 5Figure 5

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Immunology Department, Sigma Tau SpA R&D, Pomezia, Rome, Italy. rita.desantis@sigma-tau.it

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.

Show MeSH
Related in: MedlinePlus