Immuno-targeting the multifunctional CD38 using nanobody

• DOI: 10.1038/srep27055
• Publication Date: 2016-06-02T09:28:13Z
• Authors: Ting Li; Shali Qi; Mandy Unger; Yun Nan Hou; Qi Wen Deng; Jun Liu; Connie M. C. Lam; Xian Wang Wang; Du Xin; Peng Zhang; Friedrich Koch-Nolte; Quan Hao; Hongmin Zhang; Hon Cheung Lee; Yong Juan Zhao
• Keywords: Models, Molecular; Radiology, Nuclear Medicine and Imaging; Physiology; Molecular biology; Cytotoxicity; Crystallography, X-Ray; Biochemistry; Antineoplastic Agents, Immunological; Antibody Specificity; Immunology and Microbiology; 0303 health sciences; Membrane Glycoproteins; Stem cell; Life Sciences; 3. Good health; Chemistry; Antigen; Medicine; Nanobodies; Epitope; Multiple Myeloma; Protein Binding; Cell biology; Therapeutic Antibodies: Development, Engineering, and Applications; Immunology; Cancer research; Article; Cell Line; 03 medical and health sciences; In vitro; Cell Line, Tumor; Biochemistry, Genetics and Molecular Biology; Health Sciences; Genetics; Humans; Protein Interaction Domains and Motifs; Amino Acid Sequence; Biology; Lysosomal Calcium Signaling in Physiology and Pathology; Immunotoxin; FOS: Clinical medicine; Single-Domain Antibodies; ADP-ribosyl Cyclase 1; Immunotoxin Therapy for Cancer Treatment; FOS: Biological sciences; Protein Conformation, beta-Strand; Cell culture; CD34; Drug Screening Assays, Antitumor; CD38

CD38, as a cell surface antigen is highly expressed in several hematologic malignancies including multiple myeloma (MM) and has been proven to be good target for immunotherapy of the disease. CD38 also signaling enzyme responsible metabolism two novel calcium messenger molecules. To able this multifunctional protein, we generated series nanobodies against with high affinities. Crystal structures complexes were solved, identifying three separate epitopes on carboxyl domain. Chromobodies, engineered by tagging nanobody fluorescence proteins, provide fast, simple versatile tools quantifying expression. Results confirmed that was malignant MM cells compared normal white blood cells. The immunotoxin constructed splicing bacterial toxin, PE38 shows selective cytotoxicity patient-derived well lines, half maximal effective concentration reaching low 10(-11) molar. effectiveness can further increased stimulating expression using retinoid acid. These results set stage development clinical therapeutics diagnostic screening myeloma.