Sumphanapai, Thitima;
Chester, Kerry;
Sawatnatee, Surasak;
Yeung, Jenny;
Yamabhai, Montarop;
(2022)
Targeting acute myeloid cell surface using a recombinant antibody isolated from whole-cell biopanning of a phage display human scFv antibody library.
Medical Oncology
, 39
(12)
, Article 205. 10.1007/s12032-022-01806-9.
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Sumphanapai et al 2022 Targeting Acute Myeloid Cell Surface using a Recombinant Antibody Isolated from Whole Cell Biopanning of a Phage Display Human scFv Antibody.pdf - Accepted Version Download (4MB) | Preview |
Abstract
To discover new therapeutic antibodies for treatment of acute myeloid leukemia (AML) without the requirement of a known antigen, a human single-chain variable fragment (scFv) library was used to isolate novel antibody fragments recognizing HL-60 AML cells. After three rounds of biopanning, scFv-expressing phages were selected to test for binding to the target cell by flow cytometry. The clone with highest binding specificity to HL-60 cells (designated y1HL63D6) was further investigated. Fluorescent staining indicated that y1HL63D6 scFv bound to a target located on the cell surface. Whole immunoglobulin, IgG-y1HL63D6 was then generated and tested for the binding against bone marrow mononuclear cells (BMMCs) from AML patients. Significantly higher fluorescent signals were observed for some patient samples when compared to normal BMMCs or non-AML patients' BMMCs. Next, the IgG-y1HL63D6 format was tested for antibody-dependent cell cytotoxicity (ADCC). The results demonstrated that IgG-y1HL63D6 but not the control antibody, trastuzumab, could mediate specific killing of HL-60 target cells. In conclusion, our results indicate that specific antibodies can be isolated by biopanning whole cells with a non-immunized human scFv antibody phage display library and that the isolated antibody against HL-60 cells showed therapeutic potential.
| Type: | Article |
|---|---|
| Title: | Targeting acute myeloid cell surface using a recombinant antibody isolated from whole-cell biopanning of a phage display human scFv antibody library |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s12032-022-01806-9 |
| Publisher version: | https://doi.org/10.1007/s12032-022-01806-9 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Acute myeloid leukemia, Antibody, Antibody-dependent cell-mediated cytotoxicity, Cell surface, Immunotherapy, Phage display technology, Bacteriophages, Bioprospecting, Humans, Immunoglobulin G, Myeloid Cells, Single-Chain Antibodies |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10157260 |
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