CD38-specific nanobodies allow in vivo imaging of multiple myeloma under daratumumab therapy
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CD38-specific nanobodies allow in vivo imaging of multiple myeloma under daratumumab therapy. / Pape, Luca Julius; Hambach, Julia; Gebhardt, Anna Josephine; Rissiek, Björn; Stähler, Tobias; Tode, Natalie; Khan, Cerusch; Weisel, Katja; Adam, Gerhard; Koch-Nolte, Friedrich; Bannas, Peter.
In: FRONT IMMUNOL, Vol. 13, 1010270, 2022.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - CD38-specific nanobodies allow in vivo imaging of multiple myeloma under daratumumab therapy
AU - Pape, Luca Julius
AU - Hambach, Julia
AU - Gebhardt, Anna Josephine
AU - Rissiek, Björn
AU - Stähler, Tobias
AU - Tode, Natalie
AU - Khan, Cerusch
AU - Weisel, Katja
AU - Adam, Gerhard
AU - Koch-Nolte, Friedrich
AU - Bannas, Peter
N1 - Copyright © 2022 Pape, Hambach, Gebhardt, Rissiek, Stähler, Tode, Khan, Weisel, Adam, Koch-Nolte and Bannas.
PY - 2022
Y1 - 2022
N2 - RATIONALE: Recent studies have demonstrated the feasibility of CD38-specific antibody constructs for in vivo imaging of multiple myeloma. However, detecting multiple myeloma in daratumumab-pretreated patients remains difficult due to overlapping binding epitopes of the CD38-specific imaging antibody constructs and daratumumab. Therefore, the development of an alternative antibody construct targeting an epitope of CD38 distinct from that of daratumumab is needed. We report the generation of a fluorochrome-conjugated nanobody recognizing such an epitope of CD38 to detect myeloma cells under daratumumab therapy in vitro, ex vivo, and in vivo.METHODS: We conjugated the CD38-specific nanobody JK36 to the near-infrared fluorescent dye Alexa Fluor 680. The capacity of JK36AF680 to bind and detect CD38-expressing cells pretreated with daratumumab was evaluated on CD38-expressing tumor cell lines in vitro, on primary myeloma cells from human bone marrow biopsies ex vivo, and in a mouse tumor model in vivo.RESULTS: Fluorochrome-labeled nanobody JK36AF680 showed specific binding to CD38-expressing myeloma cells pretreated with daratumumab in vitro and ex vivo and allowed for specific imaging of CD38-expressing xenografts in daratumumab-pretreated mice in vivo.CONCLUSIONS: Our study demonstrates that a nanobody recognizing a distinct, non-overlapping epitope of CD38 allows the specific detection of myeloma cells under daratumumab therapy in vitro, ex vivo, and in vivo.
AB - RATIONALE: Recent studies have demonstrated the feasibility of CD38-specific antibody constructs for in vivo imaging of multiple myeloma. However, detecting multiple myeloma in daratumumab-pretreated patients remains difficult due to overlapping binding epitopes of the CD38-specific imaging antibody constructs and daratumumab. Therefore, the development of an alternative antibody construct targeting an epitope of CD38 distinct from that of daratumumab is needed. We report the generation of a fluorochrome-conjugated nanobody recognizing such an epitope of CD38 to detect myeloma cells under daratumumab therapy in vitro, ex vivo, and in vivo.METHODS: We conjugated the CD38-specific nanobody JK36 to the near-infrared fluorescent dye Alexa Fluor 680. The capacity of JK36AF680 to bind and detect CD38-expressing cells pretreated with daratumumab was evaluated on CD38-expressing tumor cell lines in vitro, on primary myeloma cells from human bone marrow biopsies ex vivo, and in a mouse tumor model in vivo.RESULTS: Fluorochrome-labeled nanobody JK36AF680 showed specific binding to CD38-expressing myeloma cells pretreated with daratumumab in vitro and ex vivo and allowed for specific imaging of CD38-expressing xenografts in daratumumab-pretreated mice in vivo.CONCLUSIONS: Our study demonstrates that a nanobody recognizing a distinct, non-overlapping epitope of CD38 allows the specific detection of myeloma cells under daratumumab therapy in vitro, ex vivo, and in vivo.
KW - Humans
KW - Animals
KW - Mice
KW - Multiple Myeloma/diagnostic imaging
KW - Single-Domain Antibodies
KW - ADP-ribosyl Cyclase 1/metabolism
KW - Fluorescent Dyes
KW - Epitopes
U2 - 10.3389/fimmu.2022.1010270
DO - 10.3389/fimmu.2022.1010270
M3 - SCORING: Journal article
C2 - 36389758
VL - 13
JO - FRONT IMMUNOL
JF - FRONT IMMUNOL
SN - 1664-3224
M1 - 1010270
ER -