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Nanobody-based CD38-specific heavy chain antibodies induce killing of multiple myeloma and other hematological malignancies

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Nanobody-based CD38-specific heavy chain antibodies induce killing of multiple myeloma and other hematological malignancies. / Schriewer, Levin; Schütze, Kerstin; Petry, Katharina; Hambach, Julia; Fumey, William; Koenigsdorf, Julia; Baum, Natalie; Menzel, Stephan; Rissiek, Björn; Riecken, Kristoffer; Fehse, Boris; Röckendorf, Jana Larissa; Schmid, Joanna; Albrecht, Birte; Pinnschmidt, Hans; Ayuk, Francis; Kröger, Nicolaus; Binder, Mascha; Schuch, Gunter; Hansen, Timon; Haag, Friedrich; Adam, Gerhard; Koch-Nolte, Friedrich; Bannas, Peter.

in: THERANOSTICS, Jahrgang 10, Nr. 6, 2020, S. 2645-2658.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Schriewer, L, Schütze, K, Petry, K, Hambach, J, Fumey, W, Koenigsdorf, J, Baum, N, Menzel, S, Rissiek, B, Riecken, K, Fehse, B, Röckendorf, JL, Schmid, J, Albrecht, B, Pinnschmidt, H, Ayuk, F, Kröger, N, Binder, M, Schuch, G, Hansen, T, Haag, F, Adam, G, Koch-Nolte, F & Bannas, P 2020, 'Nanobody-based CD38-specific heavy chain antibodies induce killing of multiple myeloma and other hematological malignancies', THERANOSTICS, Jg. 10, Nr. 6, S. 2645-2658. https://doi.org/10.7150/thno.38533

APA

Schriewer, L., Schütze, K., Petry, K., Hambach, J., Fumey, W., Koenigsdorf, J., Baum, N., Menzel, S., Rissiek, B., Riecken, K., Fehse, B., Röckendorf, J. L., Schmid, J., Albrecht, B., Pinnschmidt, H., Ayuk, F., Kröger, N., Binder, M., Schuch, G., ... Bannas, P. (2020). Nanobody-based CD38-specific heavy chain antibodies induce killing of multiple myeloma and other hematological malignancies. THERANOSTICS, 10(6), 2645-2658. https://doi.org/10.7150/thno.38533

Vancouver

Schriewer L, Schütze K, Petry K, Hambach J, Fumey W, Koenigsdorf J et al. Nanobody-based CD38-specific heavy chain antibodies induce killing of multiple myeloma and other hematological malignancies. THERANOSTICS. 2020;10(6):2645-2658. https://doi.org/10.7150/thno.38533

Bibtex

@article{844fa88647024fc0b18fa227cc53ce2f,
title = "Nanobody-based CD38-specific heavy chain antibodies induce killing of multiple myeloma and other hematological malignancies",
abstract = "Rationale: CD38 is a target for the therapy of multiple myeloma (MM) with monoclonal antibodies such as daratumumab and isatuximab. Since MM patients exhibit a high rate of relapse, the development of new biologics targeting alternative CD38 epitopes is desirable. The discovery of single-domain antibodies (nanobodies) has opened the way for a new generation of antitumor therapeutics. We report the generation of nanobody-based humanized IgG1 heavy chain antibodies (hcAbs) with a high specificity and affinity that recognize three different and non-overlapping epitopes of CD38 and compare their cytotoxicity against CD38-expressing hematological cancer cells in vitro, ex vivo and in vivo. Methods: We generated three humanized hcAbs (WF211-hcAb, MU1067-hcAb, JK36-hcAb) that recognize three different non-overlapping epitopes (E1, E2, E3) of CD38 by fusion of llama-derived nanobodies to the hinge- and Fc-domains of human IgG1. WF211-hcAb shares the binding epitope E1 with daratumumab. We compared the capacity of these CD38-specific hcAbs and daratumumab to induce CDC and ADCC in CD38-expressing tumor cell lines in vitro and in patient MM cells ex vivo as well as effects on xenograft tumor growth and survival in vivo. Results: CD38-specific heavy chain antibodies (WF211-hcAb, MU1067-hcAb, JK36-hcAb) potently induced antibody-dependent cellular cytotoxicity (ADCC) in CD38-expressing tumor cell lines and in primary patient MM cells, but only little if any complement-dependent cytotoxicity (CDC). In vivo, CD38-specific heavy chain antibodies significantly reduced the growth of systemic lymphomas and prolonged survival of tumor bearing SCID mice. Conclusions: CD38-specific nanobody-based humanized IgG1 heavy chain antibodies mediate cytotoxicity against CD38-expressing hematological cancer cells in vitro, ex vivo and in vivo. These promising results of our study indicate that CD38-specific hcAbs warrant further clinical development as therapeutics for multiple myeloma and other hematological malignancies.",
author = "Levin Schriewer and Kerstin Sch{\"u}tze and Katharina Petry and Julia Hambach and William Fumey and Julia Koenigsdorf and Natalie Baum and Stephan Menzel and Bj{\"o}rn Rissiek and Kristoffer Riecken and Boris Fehse and R{\"o}ckendorf, {Jana Larissa} and Joanna Schmid and Birte Albrecht and Hans Pinnschmidt and Francis Ayuk and Nicolaus Kr{\"o}ger and Mascha Binder and Gunter Schuch and Timon Hansen and Friedrich Haag and Gerhard Adam and Friedrich Koch-Nolte and Peter Bannas",
note = "{\textcopyright} The author(s).",
year = "2020",
doi = "10.7150/thno.38533",
language = "English",
volume = "10",
pages = "2645--2658",
journal = "THERANOSTICS",
issn = "1838-7640",
publisher = "Ivyspring International Publisher",
number = "6",

}

RIS

TY - JOUR

T1 - Nanobody-based CD38-specific heavy chain antibodies induce killing of multiple myeloma and other hematological malignancies

AU - Schriewer, Levin

AU - Schütze, Kerstin

AU - Petry, Katharina

AU - Hambach, Julia

AU - Fumey, William

AU - Koenigsdorf, Julia

AU - Baum, Natalie

AU - Menzel, Stephan

AU - Rissiek, Björn

AU - Riecken, Kristoffer

AU - Fehse, Boris

AU - Röckendorf, Jana Larissa

AU - Schmid, Joanna

AU - Albrecht, Birte

AU - Pinnschmidt, Hans

AU - Ayuk, Francis

AU - Kröger, Nicolaus

AU - Binder, Mascha

AU - Schuch, Gunter

AU - Hansen, Timon

AU - Haag, Friedrich

AU - Adam, Gerhard

AU - Koch-Nolte, Friedrich

AU - Bannas, Peter

N1 - © The author(s).

PY - 2020

Y1 - 2020

N2 - Rationale: CD38 is a target for the therapy of multiple myeloma (MM) with monoclonal antibodies such as daratumumab and isatuximab. Since MM patients exhibit a high rate of relapse, the development of new biologics targeting alternative CD38 epitopes is desirable. The discovery of single-domain antibodies (nanobodies) has opened the way for a new generation of antitumor therapeutics. We report the generation of nanobody-based humanized IgG1 heavy chain antibodies (hcAbs) with a high specificity and affinity that recognize three different and non-overlapping epitopes of CD38 and compare their cytotoxicity against CD38-expressing hematological cancer cells in vitro, ex vivo and in vivo. Methods: We generated three humanized hcAbs (WF211-hcAb, MU1067-hcAb, JK36-hcAb) that recognize three different non-overlapping epitopes (E1, E2, E3) of CD38 by fusion of llama-derived nanobodies to the hinge- and Fc-domains of human IgG1. WF211-hcAb shares the binding epitope E1 with daratumumab. We compared the capacity of these CD38-specific hcAbs and daratumumab to induce CDC and ADCC in CD38-expressing tumor cell lines in vitro and in patient MM cells ex vivo as well as effects on xenograft tumor growth and survival in vivo. Results: CD38-specific heavy chain antibodies (WF211-hcAb, MU1067-hcAb, JK36-hcAb) potently induced antibody-dependent cellular cytotoxicity (ADCC) in CD38-expressing tumor cell lines and in primary patient MM cells, but only little if any complement-dependent cytotoxicity (CDC). In vivo, CD38-specific heavy chain antibodies significantly reduced the growth of systemic lymphomas and prolonged survival of tumor bearing SCID mice. Conclusions: CD38-specific nanobody-based humanized IgG1 heavy chain antibodies mediate cytotoxicity against CD38-expressing hematological cancer cells in vitro, ex vivo and in vivo. These promising results of our study indicate that CD38-specific hcAbs warrant further clinical development as therapeutics for multiple myeloma and other hematological malignancies.

AB - Rationale: CD38 is a target for the therapy of multiple myeloma (MM) with monoclonal antibodies such as daratumumab and isatuximab. Since MM patients exhibit a high rate of relapse, the development of new biologics targeting alternative CD38 epitopes is desirable. The discovery of single-domain antibodies (nanobodies) has opened the way for a new generation of antitumor therapeutics. We report the generation of nanobody-based humanized IgG1 heavy chain antibodies (hcAbs) with a high specificity and affinity that recognize three different and non-overlapping epitopes of CD38 and compare their cytotoxicity against CD38-expressing hematological cancer cells in vitro, ex vivo and in vivo. Methods: We generated three humanized hcAbs (WF211-hcAb, MU1067-hcAb, JK36-hcAb) that recognize three different non-overlapping epitopes (E1, E2, E3) of CD38 by fusion of llama-derived nanobodies to the hinge- and Fc-domains of human IgG1. WF211-hcAb shares the binding epitope E1 with daratumumab. We compared the capacity of these CD38-specific hcAbs and daratumumab to induce CDC and ADCC in CD38-expressing tumor cell lines in vitro and in patient MM cells ex vivo as well as effects on xenograft tumor growth and survival in vivo. Results: CD38-specific heavy chain antibodies (WF211-hcAb, MU1067-hcAb, JK36-hcAb) potently induced antibody-dependent cellular cytotoxicity (ADCC) in CD38-expressing tumor cell lines and in primary patient MM cells, but only little if any complement-dependent cytotoxicity (CDC). In vivo, CD38-specific heavy chain antibodies significantly reduced the growth of systemic lymphomas and prolonged survival of tumor bearing SCID mice. Conclusions: CD38-specific nanobody-based humanized IgG1 heavy chain antibodies mediate cytotoxicity against CD38-expressing hematological cancer cells in vitro, ex vivo and in vivo. These promising results of our study indicate that CD38-specific hcAbs warrant further clinical development as therapeutics for multiple myeloma and other hematological malignancies.

U2 - 10.7150/thno.38533

DO - 10.7150/thno.38533

M3 - SCORING: Journal article

C2 - 32194826

VL - 10

SP - 2645

EP - 2658

JO - THERANOSTICS

JF - THERANOSTICS

SN - 1838-7640

IS - 6

ER -