TY - JOUR
T1 - 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
AU - Lee, Ji Hyun
AU - Kim, Ji Woong
AU - Yang, Ha Rim
AU - Song, Seong Won
AU - Lee, Song Jae
AU - Jeon, Yeongha
AU - Ju, Anna
AU - Lee, Narim
AU - Kim, Min Gu
AU - Kim, Minjoo
AU - Hwang, Kyusang
AU - Yoon, Jin Hwan
AU - Shim, Hyunbo
AU - Lee, Sukmook
N1 - Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/7/1
Y1 - 2022/7/1
N2 - 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.
AB - 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.
KW - MF‐CADM1
KW - T cell
KW - cell death
KW - fully human antibody
KW - small cell lung cancer
UR - http://www.scopus.com/inward/record.url?scp=85132279600&partnerID=8YFLogxK
U2 - 10.3390/ijms23136895
DO - 10.3390/ijms23136895
M3 - Article
C2 - 35805896
AN - SCOPUS:85132279600
SN - 1661-6596
VL - 23
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 13
M1 - 6895
ER -