title: Monoclonal antibodies targeting non-small cell lung cancer stem-like cells by multipotent cancer stem cell monoclonal antibody library.
abstract: Cancer stem cells (CSCs) are a rare subset of cancer cells that play a significant role in cancer initiation, spreading, and recurrence. In this study, a subpopulation of lung cancer stem-like cells (LCSLCs) was identified from non-small cell lung carcinoma cell lines, SPCA-1 and A549, using serum-free suspension sphere-forming culture method. A monoclonal antibody library was constructed using immunized BLAB/c mice with the multipotent CSC cell line T3A-A3. Flow cytometry analysis showed that 33 mAbs targeted antigens can be enriched in sphere cells compared with the parental cells of SPCA-1 and A549 cell lines. Then, we performed functional antibody screening including sphere-forming inhibiting and invasion inhibiting assay. The results showed that two antibodies, 12C7 and 9B8, notably suppressed the self-renewal and invasion of LCSLCs. Fluorescence-activated cell sorting (FACs) found that the positive cells recognized by mAbs, 12C7 or 9B8, displayed features of LCSLCs. Interestingly, we found that these two antibodies recognized different subsets of cells and their combination effect was superior to the individual effect both in vitro and in vivo. Tissue microarrays were applied to detect the expression of the antigens targeted by these two antibodies. The positive expression of 12C7 and 9B8 targeted antigen was 84.4 and 82.5%, respectively, which was significantly higher than that in the non-tumor lung tissues. In conclusion, we screened two potential therapeutic antibodies that target different subsets of LCSLCs.
authors.affiliation: National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China.
authors.forename: Kaiyue
authors.initials: K
authors.lastname: Cao
authors.affiliation: National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China.
authors.forename: Yunzhi
authors.initials: Y
authors.lastname: Pan
authors.affiliation: National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China.
authors.forename: Long
authors.initials: L
authors.lastname: Yu
authors.affiliation: National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Shu
authors.affiliation: National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China.
authors.forename: Linxin
authors.initials: L
authors.lastname: Sun
authors.affiliation: National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China.
authors.forename: Lichao
authors.initials: L
authors.lastname: Sun
authors.affiliation: National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Yang
authors.affiliation: National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Ran
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015723:Gene Library; D006801:Humans; D007114:Immunization; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000276:immunology; D046888:Tissue Array Analysis; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal