Although the 5-year survival rate of chronic lymphocytic leukemia (CLL) patients has risen to >80%, the only potentially curative treatment is allogeneic hematopoietic stem cell transplantation (alloHSCT). To identify possible new monoclonal antibody (mAb) drugs and targets for CLL, we previously developed a phage display–based human mAb platform to mine the antibody repertoire of patients who responded to alloHSCT. We had selected a group of highly homologous post-alloHSCT mAbs that bound to an unknown CLL cell surface antigen. Here, we show through next-generation sequencing of cDNAs encoding variable heavy-chain domains that these mAbs had a relative abundance of 0.1% in the post-alloHSCT antibody repertoire and were enriched 1,000-fold after three rounds of selection on primary CLL cells. Based on differential RNA-seq and a cell microarray screening technology for discovering human cell surface antigens, we now identify their antigen as Siglec-6. We verified this finding by flow cytometry, ELISA, siRNA knockdown, and surface plasmon resonance. Siglec-6 was broadly expressed in CLL and could be a potential target for antibody-based therapeutic interventions. Our study reaffirms the utility of post-alloHSCT antibody drug and target discovery. Cancer
CITATION STYLE
Chang, J., Peng, H., Shaffer, B. C., Baskar, S., Wecken, I. C., Cyr, M. G., … Rader, C. (2018). SiGleC-6 on chronic lymphocytic leukemia cells is a target for post-allogeneic hematopoietic stem cell transplantation antibodies. Cancer Immunology Research, 6(9), 1008–1013. https://doi.org/10.1158/2326-6066.CIR-18-0102
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