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- Title
Efficient targeting of CD13 on cancer cells by the immunotoxin scFv13-ETA′ and the bispecific scFv [13xds16].
- Authors
Grieger, Elena; Gresch, Gerrit; Niesen, Judith; Woitok, Mira; Barth, Stefan; Fischer, Rainer; Fendel, Rolf; Stein, Christoph
- Abstract
Purpose: 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. Methods: 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. Results: 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 (IC 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. Conclusion: 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
CD134 antigen; ANTIBODY-toxin conjugates; CANCER chemotherapy; EXOTOXIN; PSEUDOMONAS aeruginosa; APOPTOSIS
- Publication
Journal of Cancer Research & Clinical Oncology, 2017, Vol 143, Issue 11, p2159
- ISSN
0171-5216
- Publication type
Article
- DOI
10.1007/s00432-017-2468-5