Abstract | PURPOSE: METHODS: The ITs and corresponding imaging probes were tested in vitro against four solid tumor entities ( rhabdomyosarcoma, breast, prostate and pancreatic cancer). Specific binding and internalization of the ITs scFv2112-ETA' (from cetuximab) and scFv1711-ETA' (from panitumumab) were demonstrated by flow cytometry and for the scFv-SNAP-tag imaging probes by live cell imaging. Cytotoxic potential of the ITs was analyzed in cell viability and apoptosis assays. Binding of the ITs was proofed ex vivo on rhabdomyosarcoma, prostate and breast cancer formalin-fixed paraffin-embedded biopsies. RESULTS: Both novel ITs showed significant pro-apoptotic and anti-proliferative effects toward the target cells, achieving IC50 values of 4 pM (high EGFR expression) to 460 pM (moderate EGFR expression). Additionally, rapid internalization and specific in vitro and ex vivo binding on patient tissue were confirmed. CONCLUSIONS: These data demonstrate the potent therapeutic activity of two novel EGFR-specific ETA'-based ITs. Both molecules are promising candidates for further development toward clinical use in the treatment of various solid tumors to supplement the existing therapeutic regimes.
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Authors | Judith Niesen, Christoph Stein, Hannes Brehm, Grit Hehmann-Titt, Rolf Fendel, Georg Melmer, Rainer Fischer, Stefan Barth |
Journal | Journal of cancer research and clinical oncology
(J Cancer Res Clin Oncol)
Vol. 141
Issue 12
Pg. 2079-95
(Dec 2015)
ISSN: 1432-1335 [Electronic] Germany |
PMID | 25899161
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- Antineoplastic Agents
- Bacterial Toxins
- Exotoxins
- Immunologic Factors
- Immunotoxins
- Single-Chain Antibodies
- Virulence Factors
- Panitumumab
- ADP Ribose Transferases
- EGFR protein, human
- ErbB Receptors
- Cetuximab
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Topics |
- ADP Ribose Transferases
(metabolism)
- Antibodies, Monoclonal
(pharmacology)
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects)
- Bacterial Toxins
(metabolism)
- Blotting, Western
- Cell Proliferation
(drug effects)
- Cetuximab
(pharmacology)
- ErbB Receptors
(antagonists & inhibitors)
- Exotoxins
(metabolism)
- Flow Cytometry
- Humans
- Immunologic Factors
(pharmacology)
- Immunotoxins
(pharmacology)
- Neoplasms
(drug therapy, immunology, metabolism, pathology)
- Panitumumab
- Single-Chain Antibodies
(pharmacology)
- Tumor Cells, Cultured
- Virulence Factors
(metabolism)
- Pseudomonas aeruginosa Exotoxin A
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