Phase I/II clinical trial of the humanized anti-EGF-r monoclonal antibody h-R3 labelled with 99mTc in patients with tumour of epithelial origin

La, Torres; Perera, Alejandro; Jf, Batista; Hernández, Andrea; Crombet, Tania; Ramos, Mayra; Neninger, Elia; Pérez, Mariela León; El, Sánchez; Romero, Susana; Aguilar,; Ma, Coca; Iznaga-Escobar, Normando

doi:10.1097/00006231-200512000-00002

Cited by 27 publications

(16 citation statements)

References 15 publications

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“…accompanied with relatively high signals from liver and the gastrointestinal tract. Various imaging studies have been undertaken with other monoclonal antibodies targeting EGFR or with alternative radionuclide labels [41][42][43][44][45][46]. Biodistribution studies with most of these EGFR-binding monoclonal antibodies also indicate high liver uptake and relatively low tumor-to-blood ratios with an optimal biodistribution for tumor detection at one day after tracer administration or later [46][47][48][49][50][51][52][53].…”

Section: Discussionmentioning

confidence: 99%

SPECT Imaging with 99mTc-Labeled EGFR-Specific Nanobody for In Vivo Monitoring of EGFR Expression

et al. 2008

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Section: Discussionmentioning

confidence: 99%

SPECT Imaging with 99mTc-Labeled EGFR-Specific Nanobody for In Vivo Monitoring of EGFR Expression

et al. 2008

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“…Several clinical trials are being evaluated. Torres et al (2005) have constructed a humanized anti-EGFR mAb, labeled with 99 Tc, which emits b particles. This conjugate demonstrated promising results with a sensitivity of 76.5% and a specificity of 100%.…”

Section: Radioisotopes Immunoconjugatesmentioning

confidence: 99%

Novel antibodies as anticancer agents

2007

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In recent years antibodies, whether generated by traditional hybridoma technology or by recombinant DNA strategies, have evolved from Paul Ehrlich's 'magic bullets' to a modern age 'guided missile'. In the recent years of immunologic research, we are witnessing development in the fields of antigen screening and protein engineering in order to create specific anticancer remedies. The developments in the field of recombinant DNA, protein engineering and cancer biology have let us gain insight into many cancer-related mechanisms. Moreover, novel techniques have facilitated tools allowing unique distinction between malignantly transformed cells, and regular ones. This understanding has paved the way for the rational design of a new age of pharmaceuticals: monoclonal antibodies and their fragments. Antibodies can select antigens on both a specific and a high-affinity account, and further implementation of these qualities is used to target cancer cells by specifically identifying exogenous antigens of cancer cell populations. The structure of the antibody provides plasticity resonating from its functional sites. This review will screen some of the many novel antibodies and antibody-based approaches that are being currently developed for clinical applications as the new generation of anticancer agents.

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“…There are several studies suggesting that PET might be the optimal tool (9,10,24). This technique, however, entails the combined application of a pair of isotopes such as the diagnostic b 1 -emitting radionuclide 86 Y and the therapeutic b 2 -emitting radionuclide 90 Y, both immobilized by the same mAb to be performed in 2 consecutive procedures: a diagnostic investigation with PET before the actual treatment.…”

Section: Discussionmentioning

confidence: 99%

Inactivation of HNSCC Cells by ⁹⁰Y-Labeled Cetuximab Strictly Depends on the Number of Induced DNA Double-Strand Breaks

et al. 2013

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Radioimmunotherapy is considered to have great potential for efficient and highly specific treatment of tumors. The aim of this study was to determine the efficacy of radioimmunotherapy when using 90 Y-labeled cetuximab and to determine to what degree induction and repair of DNA double-strand breaks (DSBs) are decisive for this approach. Methods: This study was performed with 9 cell lines of squamous cell carcinoma of the head and neck (HNSCC) differing strongly in epidermal growth factor receptor (EGFR) expression. The radionuclide 90 Y was coupled by the chelator trans-cyclohexyl-diethylene-triaminepentaacetic acid (CHX-A$-DTPA)/linker construct to the EGFR-directed antibody cetuximab to yield 90 Y-Y-CHX-A$-DTPA-cetuximab with a specific activity of approximately 1.2 GBq/mg. EGFR expression was determined by immunofluorescence and Western blotting, cetuximab binding by fluorescence-activated cell sorter analysis, the number of DSBs by immunofluorescence staining gH2AX/53BP1-positive repair foci, and cell survival by colony formation. Results: For the 9 HNSCC cell lines, cetuximab binding correlated with the amount of EGFR present in the cell membrane (r 2 5 0.967, P , 0.001). When cells were exposed to 90 Y-Y-CHX-A$-DTPA-cetuximab, the number of induced DSBs increased linearly with time (r 2 5 0.968, P 5 0.016). This number was found to correlate with the amount of membranous EGFR (r 2 5 0.877, P 5 0.006). Most DSBs were repaired during incubation at 37°C, but the small number of remaining DSBs still correlated with the amount of membranous EGFR (24 h: r 2 5 0.977, P , 0.001; 48 h: r 2 5 0.947, P , 0.001). Exposure to 90 Y-Y-CHX-A$-DTPA-cetuximab also resulted in efficient cell killing, whereby the extent of cell killing correlated strongly with the respective number of remaining DSBs (r 2 5 0.989, P , 0.001) and with the amount of membranous EGFR (r 2 5 0.967, P , 0.001). No cell killing was observed for UTSCC15 cells with low EGFR expression, in contrast to the strong reduction of 86% measured for UTSCC14 cells showing a strong overexpression of EGFR. Conclusion: 90 Y-Y-CHX-A$-DTPA-cetuximab affected cell survival through the induction of DSBs. This treatment was especially efficient for HNSCC cells strongly overexpressing EGFR, whereas no effect was seen for cells with low levels of EGFR expression. Therefore, EGFR-directed radioimmunotherapy using 90 Y-Y-CHX-A$-DTPA-cetuximab appears to be a powerful tool that can be used to inactivate tumors with strong EGFR overexpression, which are often characterized by a pronounced radioresistance.

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Phase I/II clinical trial of the humanized anti-EGF-r monoclonal antibody h-R3 labelled with 99mTc in patients with tumour of epithelial origin

Abstract: The results of this study suggest that Tc-h-R3 could be used in patients in a safe and effective way, for the diagnosis of epithelial-derived tumours at the two evaluated dose levels.

Cited by 27 publications

References 15 publications

SPECT Imaging with 99mTc-Labeled EGFR-Specific Nanobody for In Vivo Monitoring of EGFR Expression

SPECT Imaging with 99mTc-Labeled EGFR-Specific Nanobody for In Vivo Monitoring of EGFR Expression

Novel antibodies as anticancer agents

Inactivation of HNSCC Cells by ⁹⁰Y-Labeled Cetuximab Strictly Depends on the Number of Induced DNA Double-Strand Breaks

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Phase I/II clinical trial of the humanized anti-EGF-r monoclonal antibody h-R3 labelled with 99mTc in patients with tumour of epithelial origin

Abstract: The results of this study suggest that Tc-h-R3 could be used in patients in a safe and effective way, for the diagnosis of epithelial-derived tumours at the two evaluated dose levels.

Cited by 27 publications

References 15 publications

SPECT Imaging with 99mTc-Labeled EGFR-Specific Nanobody for In Vivo Monitoring of EGFR Expression

SPECT Imaging with 99mTc-Labeled EGFR-Specific Nanobody for In Vivo Monitoring of EGFR Expression

Novel antibodies as anticancer agents

Inactivation of HNSCC Cells by 90Y-Labeled Cetuximab Strictly Depends on the Number of Induced DNA Double-Strand Breaks

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Inactivation of HNSCC Cells by ⁹⁰Y-Labeled Cetuximab Strictly Depends on the Number of Induced DNA Double-Strand Breaks