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A Fully-Human Antibody Specifically Targeting a Membrane-Bound Fragment of CADM1 Potentiates the T Cell-Mediated Death of Human Small-Cell Lung Cancer Cells
- Title
- A Fully-Human Antibody Specifically Targeting a Membrane-Bound Fragment of CADM1 Potentiates the T Cell-Mediated Death of Human Small-Cell Lung Cancer Cells
- Authors
- Lee, Ji Hyun; Kim, Ji Woong; Yang, Ha Rim; Song, Seong-Won; Lee, Song-Jae; Jeon, Yeongha; Ju, Anna; Lee, Narim; Kim, Min-Gu; Kim, Minjoo; Hwang, Kyusang; Yoon, Jin Hwan; Shim, Hyunbo; Lee, Sukmook
- Ewha Authors
- 심현보
- SCOPUS Author ID
- 심현보
- Issue Date
- 2022
- Journal Title
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
- ISSN
- 1422-0067
- Citation
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES vol. 23, no. 13
- Keywords
- fully human antibody; MF-CADM1; cell death; T cell; small cell lung cancer
- Publisher
- MDPI
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Small-cell lung cancer (SCLC) is the most aggressive form of lung cancer and the leading cause of global cancer-related mortality. Despite the earlier identification of membrane-proximal cleavage of cell adhesion molecule 1 (CADM1) in cancers, the role of the membrane-bound fragment of CAMD1 (MF-CADM1) is yet to be clearly identified. In this study, we first isolated MF-CADM1-specific fully human single-chain variable fragments (scFvs) from the human synthetic scFv antibody library using the phage display technology. Following the selected scFv conversion to human immunoglobulin G1 (IgG1) scFv-Fc antibodies (K103.1-4), multiple characterization studies, including antibody cross-species reactivity, purity, production yield, and binding affinity, were verified. Finally, via intensive in vitro efficacy and toxicity evaluation studies, we identified K103.3 as a lead antibody that potently promotes the death of human SCLC cell lines, including NCI-H69, NCI-H146, and NCI-H187, by activated Jurkat T cells without severe endothelial toxicity. Taken together, these findings suggest that antibody-based targeting of MF-CADM1 may be an effective strategy to potentiate T cell-mediated SCLC death, and MF-CADM1 may be a novel potential therapeutic target in SCLC for antibody therapy.
- DOI
- 10.3390/ijms23136895
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
- Files in This Item:
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ijms-23-06895-v2.pdf(2.92 MB)
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