Immuno-targeting the multifunctional CD38 using nanobody
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Immuno-targeting the multifunctional CD38 using nanobody. / Li, Ting; Qi, Shali; Unger, Mandy; Hou, Yun Nan; Deng, Qi Wen; Liu, Jun; Lam, Connie M C; Wang, Xian Wang; Xin, Du; Zhang, Peng; Nolte, Friedrich; Hao, Quan; Zhang, Hongmin; Lee, Hon Cheung; Zhao, Yong Juan.
in: SCI REP-UK, Jahrgang 6, 02.06.2016, S. 27055.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Immuno-targeting the multifunctional CD38 using nanobody
AU - Li, Ting
AU - Qi, Shali
AU - Unger, Mandy
AU - Hou, Yun Nan
AU - Deng, Qi Wen
AU - Liu, Jun
AU - Lam, Connie M C
AU - Wang, Xian Wang
AU - Xin, Du
AU - Zhang, Peng
AU - Nolte, Friedrich
AU - Hao, Quan
AU - Zhang, Hongmin
AU - Lee, Hon Cheung
AU - Zhao, Yong Juan
PY - 2016/6/2
Y1 - 2016/6/2
N2 - CD38, as a cell surface antigen is highly expressed in several hematologic malignancies including multiple myeloma (MM) and has been proven to be a good target for immunotherapy of the disease. CD38 is also a signaling enzyme responsible for the metabolism of two novel calcium messenger molecules. To be able to target this multifunctional protein, we generated a series of nanobodies against CD38 with high affinities. Crystal structures of the complexes of CD38 with the nanobodies were solved, identifying three separate epitopes on the carboxyl domain. Chromobodies, engineered by tagging the nanobody with fluorescence proteins, provide fast, simple and versatile tools for quantifying CD38 expression. Results confirmed that CD38 was highly expressed in malignant MM cells compared with normal white blood cells. The immunotoxin constructed by splicing the nanobody with a bacterial toxin, PE38 shows highly selective cytotoxicity against patient-derived MM cells as well as the cell lines, with half maximal effective concentration reaching as low as 10(-11) molar. The effectiveness of the immunotoxin can be further increased by stimulating CD38 expression using retinoid acid. These results set the stage for the development of clinical therapeutics as well as diagnostic screening for myeloma.
AB - CD38, as a cell surface antigen is highly expressed in several hematologic malignancies including multiple myeloma (MM) and has been proven to be a good target for immunotherapy of the disease. CD38 is also a signaling enzyme responsible for the metabolism of two novel calcium messenger molecules. To be able to target this multifunctional protein, we generated a series of nanobodies against CD38 with high affinities. Crystal structures of the complexes of CD38 with the nanobodies were solved, identifying three separate epitopes on the carboxyl domain. Chromobodies, engineered by tagging the nanobody with fluorescence proteins, provide fast, simple and versatile tools for quantifying CD38 expression. Results confirmed that CD38 was highly expressed in malignant MM cells compared with normal white blood cells. The immunotoxin constructed by splicing the nanobody with a bacterial toxin, PE38 shows highly selective cytotoxicity against patient-derived MM cells as well as the cell lines, with half maximal effective concentration reaching as low as 10(-11) molar. The effectiveness of the immunotoxin can be further increased by stimulating CD38 expression using retinoid acid. These results set the stage for the development of clinical therapeutics as well as diagnostic screening for myeloma.
KW - Journal Article
U2 - 10.1038/srep27055
DO - 10.1038/srep27055
M3 - SCORING: Journal article
C2 - 27251573
VL - 6
SP - 27055
JO - SCI REP-UK
JF - SCI REP-UK
SN - 2045-2322
ER -