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Efficient targeting of CD13 on cancer cells by the immunotoxin scFv13-ETA' and the bispecific scFv [13xds16]
- Source :
- Journal of cancer research and clinical oncology. 143(11)
- Publication Year :
- 2017
-
Abstract
- Treatment of cancer using standard chemotherapy still offers a poor prognosis combined with severe side effects. Novel antibody-based therapies have been shown to overcome low efficiency and lack of selectivity by targeting cancer-associated antigens, such as aminopeptidase CD13. We isolated a high-affinity CD13-specific single-chain fragment variable (scFv13) from a phage display library of V-genes from mice immunized with soluble antigen. An immunotoxin comprising the scFv13 and a truncated version of the exotoxin A of Pseudomonas aeruginosa (ETA′, scFv13–ETA′) and a bispecific scFv targeting CD13 and CD16 simultaneously (bsscFv[13xds16]) was generated and investigated for their therapeutic potential. Both fusion proteins bound specifically to target cells with high affinity. Furthermore, scFv13–ETA′ inhibited the proliferation of human cancer cell lines efficiently at low concentrations (IC50 values of 408 pM–7 nM) and induced apoptosis (40–85% of target cells). The bsscFv triggered dose-dependent antibody-dependent cell-mediated cytotoxicity, resulting in the lysis of up to 23.9% A2058 cells, 18.0% MDA-MB-468 cells and 19.1% HL-60 cells. The provided data demonstrate potent therapeutic activity of the scFv13–ETA′ and the bsscFv[13xds16]. The CD13-specific scFv is therefore suitable for the direct and specific delivery of both cytotoxic agents and effector cells to cancer-derived cells, making it ideal for further therapeutic evaluation.
- Subjects :
- 0301 basic medicine
Cancer Research
Phage display
Virulence Factors
Bacterial Toxins
Exotoxins
Apoptosis
CD13 Antigens
03 medical and health sciences
0302 clinical medicine
Antigen
Immunotoxin
Neoplasms
Antibodies, Bispecific
Tumor Cells, Cultured
Single-chain variable fragment
Pseudomonas exotoxin
Humans
Cytotoxicity
Cell Proliferation
ADP Ribose Transferases
biology
Chemistry
Immunotoxins
General Medicine
Molecular biology
Recombinant Proteins
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Cancer cell
biology.protein
Antibody
Single-Chain Antibodies
Subjects
Details
- ISSN :
- 14321335
- Volume :
- 143
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Journal of cancer research and clinical oncology
- Accession number :
- edsair.doi.dedup.....d121e3ce6dfe81f0f0d6f225495c01a4